You are here

Ilyasova, Dora

Overview:

My research is in two areas: studies of the role of oxidative status in etiology of cancer and epidemiology of glioma.
I. Oxidative Status as a Susceptibility Factor
Reactive oxygen species (ROS) are produced constantly by normal metabolism. As a result, exposure to ROS is ubiquitous, and consequently a certain level of oxidative damage is always present in any individual. To protect cells from excessive oxidation, humans, like all aerobic organisms, have developed multiple anti-oxidant defense systems. These two opposing processes – oxidation and anti-oxidant defense – determine the inner redox environment, or “oxidative status” of an individual.
Focus on Oxidative Status in Human Populations: Oxidative status can be measured by biomarkers, specifically by the levels of non-enzymatic oxidative modifications. We demonstrated that individuals differ in their oxidative status. We studied the relationships between oxidative indices and inflammation. We also showed that in contrast to the existing hypothesis, high oxidative status is associated with the lower risk of diabetes. How the levels of these biomarkers of oxidative status relate to cancer susceptibility remains unknown. This is the central theme of my research.
II. Response to Low-Dose Radiation in Studies of Cancer Susceptibility
We recently received a grant from the National Brain Foundation (Il’yasova, PI) to individual response to low-dose radiation. Studies of low-dose radiation have two important aspects. First, medical diagnostic radiation is a highly prevalent exposure to low-dose radiation. The increasing prevalence of computerized tomography (CT) scans emphasizes the question of whether diagnostic radiation has adverse health effects. Second, low-dose radiation (0.1-0.5Gy) models the low-level oxidative disturbance typical for environmental carcinogens.
In this study we use circulating mesenchymal progenitor cells (cMPC). cMPC will be isolated from different individuals, cultured, and exposed to low-dose radiation. The response is measured as percentage of cells undergoing apoptosis and as clonogenic survival. This work is perfoemd in collaboration with Dr, Michael Zalutsky (Duke University Medical Center) and Dr. Shay Soker (Wake Forest Institute for Regenerative Medicine).
III. Epidemiology of Adult Glioma
Dr. Il’yasova participates in two multi-center studies of adult glioma. The Duke Brain SPORE Epidemiological study focuses on gene environment interaction between exposure to neurocarcinogens and metabolizing enzymes. Her accomplishments include increasing response rate among cases from 50% to 74% and introducing procedure for recruitment of hospital-based controls with the response rate of 90%. Currently, she is working on several manuscripts analyzing the data obtained in this study .
Dr. Il’yasova is the PI at Duke for the international study of genetic predisposition to glioma – GLIOGENE. This study is the result of collaboration developed within the Brain Tumor Epidemiological Consortium (BTEC). As the one of the Pis of GLIOGENE and as a member of BTEC, she participated in several publications.

Positions:

Associate Consulting Professor in the Department of Community and Family Medicine

Community and Family Medicine, Prevention Research
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.S.P.H. 1999

M.S.P.H. — University of North Carolina at Chapel Hill

Ph.D. 2001

Ph.D. — University of North Carolina at Chapel Hill

Grants:

Mulit-Center Case Control Study of Malignant Glioma

Administered By
Community and Family Medicine
AwardedBy
Baylor University
Role
Principal Investigator
Start Date
September 01, 2011
End Date
December 31, 2015

Heat and Radiation Effects on Tumor Microcirculation

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
January 01, 1985
End Date
September 30, 2015

Integrating Population and Basic Science in Cancer Research

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Faculty Member
Start Date
September 01, 2009
End Date
August 31, 2015

Urinary F2-isoprostanes as a new biomarker for the risk of type 2 diabetes

Administered By
Community and Family Medicine, Prevention Research
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
February 01, 2009
End Date
January 31, 2013

Meningioma: Risk Factors and Quality of Life

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
PD/PI
Start Date
June 26, 2006
End Date
March 31, 2012

Research Training In Neuro-Oncology

Administered By
Neurosurgery, Neuro-Oncology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 15, 2005
End Date
August 31, 2010
Show More

Publications:

Urinary F2-isoprostanes and the risk of hypertension.

There is strong biological plausibility for a causal role of reactive oxygen species in vascular pathology but no direct epidemiological evidence linking elevated reactive oxygen species levels to hypertension development. We examined cross-sectional and prospective associations between oxidative status (urinary F2-isoprostanes) and hypertension in the Insulin Resistance Atherosclerosis Study cohort (n = 831).The cohort included non-Hispanic white, Hispanic, and non-Hispanic black individuals, with 252 (30%) having prevalent hypertension and 579 participants normotensive at baseline, 122 (21%) of whom developed hypertension during the 5-year follow-up. Four urinary F2-isoprostane isomers were quantified in baseline specimens using LC/MS-MS and were summarized as a composite index. Examined outcomes included hypertension status (yes/no), systolic (SBP) and diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP).Prevalent and incident hypertension were associated with greater age, Black race, impaired glucose tolerance, and greater BMI. F2-IsoP levels were lower among men and among non-Hispanic Blacks, were inversely associated with age, and were directly associated with BMI. No cross-sectional association was found between F2-isoprostanes and hypertension status (OR = 0.93, 0.77-0.12). Among the continuous measures of blood pressure only PP was associated with F2-isoprostanes at baseline (beta-coefficient = 0.99, 0.11-1.86). No prospective association was found between F2-isoprostanes and incident hypertension: OR = 0.98, 0.77-1.25. No prospective associations were found for systolic blood pressure and diastolic blood pressure, and pulse pressure. Mean arterial pressure showed an inverse association (beta-coefficient = -0.16, -0.31 to -0.01).Elevated F2-isoprostane levels do not increase the risk of hypertension.

Authors
Melton, CD; Luo, R; Wong, BJ; Spasojevic, I; Wagenknecht, LE; D'Agostino, RB; Il'yasova, D
MLA Citation
Melton, CD, Luo, R, Wong, BJ, Spasojevic, I, Wagenknecht, LE, D'Agostino, RB, and Il'yasova, D. "Urinary F2-isoprostanes and the risk of hypertension." Annals of epidemiology 27.6 (June 2017): 391-396.
PMID
28558917
Source
epmc
Published In
Annals of Epidemiology
Volume
27
Issue
6
Publish Date
2017
Start Page
391
End Page
396
DOI
10.1016/j.annepidem.2017.05.005

Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.

Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10-9, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10-10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10-11, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10-10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10-9, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10-10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10-10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10-9, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10-10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10-11, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10-9, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.

Authors
Melin, BS; Barnholtz-Sloan, JS; Wrensch, MR; Johansen, C; Il'yasova, D; Kinnersley, B; Ostrom, QT; Labreche, K; Chen, Y; Armstrong, G; Liu, Y; Eckel-Passow, JE; Decker, PA; Labussière, M; Idbaih, A; Hoang-Xuan, K; Di Stefano, A-L; Mokhtari, K; Delattre, J-Y; Broderick, P; Galan, P; Gousias, K; Schramm, J; Schoemaker, MJ; Fleming, SJ; Herms, S; Heilmann, S; Nöthen, MM; Wichmann, H-E; Schreiber, S; Swerdlow, A; Lathrop, M; Simon, M; Sanson, M; Andersson, U; Rajaraman, P; Chanock, S; Linet, M et al.
MLA Citation
Melin, BS, Barnholtz-Sloan, JS, Wrensch, MR, Johansen, C, Il'yasova, D, Kinnersley, B, Ostrom, QT, Labreche, K, Chen, Y, Armstrong, G, Liu, Y, Eckel-Passow, JE, Decker, PA, Labussière, M, Idbaih, A, Hoang-Xuan, K, Di Stefano, A-L, Mokhtari, K, Delattre, J-Y, Broderick, P, Galan, P, Gousias, K, Schramm, J, Schoemaker, MJ, Fleming, SJ, Herms, S, Heilmann, S, Nöthen, MM, Wichmann, H-E, Schreiber, S, Swerdlow, A, Lathrop, M, Simon, M, Sanson, M, Andersson, U, Rajaraman, P, Chanock, S, and Linet, M et al. "Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors." Nature genetics 49.5 (May 2017): 789-794.
PMID
28346443
Source
epmc
Published In
Nature Genetics
Volume
49
Issue
5
Publish Date
2017
Start Page
789
End Page
794
DOI
10.1038/ng.3823

African Ancestry Gradient Is Associated with Lower Systemic F2-Isoprostane Levels.

Context. Low levels of systemic F2-isoprostanes (F2-IsoP) increase the risk of diabetes and weight gain and were found in African Americans. Low F2-IsoPs could reflect an unfavorable metabolic characteristic, namely, slow mitochondrial metabolism in individuals with African ancestry. Objective. To examine differences in plasma F2-IsoPs in three groups with a priori different proportion of African ancestry: non-Hispanic Whites (NHWs), US-born African Americans (AAs), and West African immigrants (WAI). Design. Cross-sectional study. Setting. Georgia residents recruited from church communities. Participants. 218 males and females 25-74 years of age, who are self-identified as NHW (n = 83), AA (n = 56), or WAI (n = 79). Main Outcome Measure(s). Plasma F2-IsoPs quantified by gas chromatography-mass spectrometry. Results. After adjustment for age, gender, obesity, and other comorbidities, WAI had lower levels of plasma F2-IsoP than AA (beta-coefficient = -9.8, p < 0.001) and AA had lower levels than NHW (beta-coefficient = -30.3, p < 0.001). Similarly, among healthy nonobese participants, F2-IsoP levels were lowest among WAI, followed by AA, and the highest levels were among NHW. Conclusion. Plasma F2-IsoPs are inversely associated with African ancestry gradient. Additional studies are required to test whether optimization of systemic F2-IsoP levels can serve as means to improve race-specific lifestyle and pharmacological intervention targeted to obesity prevention and treatment.

Authors
Annor, F; Goodman, M; Thyagarajan, B; Okosun, I; Doumatey, A; Gower, BA; Il'yasova, D
MLA Citation
Annor, F, Goodman, M, Thyagarajan, B, Okosun, I, Doumatey, A, Gower, BA, and Il'yasova, D. "African Ancestry Gradient Is Associated with Lower Systemic F2-Isoprostane Levels." Oxidative medicine and cellular longevity 2017 (January 31, 2017): 8319176-.
PMID
28250893
Source
epmc
Published In
Oxidative Medicine and Cellular Longevity
Volume
2017
Publish Date
2017
Start Page
8319176
DOI
10.1155/2017/8319176

Distinctions in Breast Tumor Recurrence Patterns Post-Therapy among Racially Distinct Populations.

Clinical studies have revealed a higher risk of breast tumor recurrence in African-American (AA) patients compared to European-American (EA) patients, contributing to the alarming inequality in clinical outcomes among the ethnic groups. However, distinctions in recurrence patterns upon receiving hormone, radiation, and/or chemotherapy between the races remain poorly characterized.We compared patterns and rates (per 1000 cancer patients per 1 year) of recurrence following each form of treatment between AA (n = 1850) and EA breast cancer patients (n = 7931) from a cohort of patients (n = 10504) treated between 2005-2015 at Northside Hospital in Atlanta, GA.Among patients who received any combination of adjuvant therapy, AA displayed higher overall rates of recurrence than EA (p = 0.015; HR: 1.699; CI: 1.108-2.606). Furthermore, recurrence rates were higher in AA than EA among stage I (p = 0.031; HR: 1.736; CI: 1.052-2.864) and T1 classified patients (p = 0.003; HR: 2.009; CI: 1.263-3.197). Interestingly, among patients who received neoadjuvant chemotherapy, AA displayed higher rates of local recurrence than EA (p = 0.024; HR: 7.134; CI: 1.295-39.313).Our analysis revealed higher incidence rates of recurrence in AA compared to EA among patients that received any combination of adjuvant therapy. Moreover, our data demonstrates an increased risk of tumor recurrence in AA than EA among patients diagnosed with minimally invasive disease. This is the first clinical study to suggest that neoadjuvant chemotherapy improves breast cancer recurrence rates and patterns in AA.

Authors
Wright, N; Xia, J; Cantuaria, G; Klimov, S; Jones, M; Neema, P; Il'yasova, D; Krishnamurti, U; Li, X; Reid, MD; Gupta, M; Rida, PCG; Osan, R; Aneja, R
MLA Citation
Wright, N, Xia, J, Cantuaria, G, Klimov, S, Jones, M, Neema, P, Il'yasova, D, Krishnamurti, U, Li, X, Reid, MD, Gupta, M, Rida, PCG, Osan, R, and Aneja, R. "Distinctions in Breast Tumor Recurrence Patterns Post-Therapy among Racially Distinct Populations." PloS one 12.1 (January 13, 2017): e0170095-.
PMID
28085947
Source
epmc
Published In
PloS one
Volume
12
Issue
1
Publish Date
2017
Start Page
e0170095
DOI
10.1371/journal.pone.0170095

History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC).

Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox and establishes life-long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case-Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two-stage random-effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65-0.96). Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta-analyses of the literature and investigations of the potential biological mechanism, are warranted.

Authors
Amirian, ES; Scheurer, ME; Zhou, R; Wrensch, MR; Armstrong, GN; Lachance, D; Olson, SH; Lau, CC; Claus, EB; Barnholtz-Sloan, JS; Il'yasova, D; Schildkraut, J; Ali-Osman, F; Sadetzki, S; Jenkins, RB; Bernstein, JL; Merrell, RT; Davis, FG; Lai, R; Shete, S; Amos, CI; Melin, BS; Bondy, ML
MLA Citation
Amirian, ES, Scheurer, ME, Zhou, R, Wrensch, MR, Armstrong, GN, Lachance, D, Olson, SH, Lau, CC, Claus, EB, Barnholtz-Sloan, JS, Il'yasova, D, Schildkraut, J, Ali-Osman, F, Sadetzki, S, Jenkins, RB, Bernstein, JL, Merrell, RT, Davis, FG, Lai, R, Shete, S, Amos, CI, Melin, BS, and Bondy, ML. "History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC)." Cancer medicine 5.6 (June 2016): 1352-1358.
PMID
26972449
Source
epmc
Published In
Cancer Medicine
Volume
5
Issue
6
Publish Date
2016
Start Page
1352
End Page
1358
DOI
10.1002/cam4.682

Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS)

Authors
Lee, CC; Watkins, SM; Lorenzo, C; Wagenknecht, LE; Il’yasova, D; Chen, Y-DI; Haffner, SM; Hanley, AJ
MLA Citation
Lee, CC, Watkins, SM, Lorenzo, C, Wagenknecht, LE, Il’yasova, D, Chen, Y-DI, Haffner, SM, and Hanley, AJ. "Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS)." Diabetes Care 39.4 (April 2016): 582-588.
Source
crossref
Published In
Diabetes Care
Volume
39
Issue
4
Publish Date
2016
Start Page
582
End Page
588
DOI
10.2337/dc15-2284

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study.

Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk.The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema.Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma.A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental.As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention.

Authors
Amirian, ES; Zhou, R; Wrensch, MR; Olson, SH; Scheurer, ME; Il'yasova, D; Lachance, D; Armstrong, GN; McCoy, LS; Lau, CC; Claus, EB; Barnholtz-Sloan, JS; Schildkraut, J; Ali-Osman, F; Sadetzki, S; Johansen, C; Houlston, RS; Jenkins, RB; Bernstein, JL; Merrell, RT; Davis, FG; Lai, R; Shete, S; Amos, CI; Melin, BS; Bondy, ML
MLA Citation
Amirian, ES, Zhou, R, Wrensch, MR, Olson, SH, Scheurer, ME, Il'yasova, D, Lachance, D, Armstrong, GN, McCoy, LS, Lau, CC, Claus, EB, Barnholtz-Sloan, JS, Schildkraut, J, Ali-Osman, F, Sadetzki, S, Johansen, C, Houlston, RS, Jenkins, RB, Bernstein, JL, Merrell, RT, Davis, FG, Lai, R, Shete, S, Amos, CI, Melin, BS, and Bondy, ML. "Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 25.2 (February 2016): 282-290.
PMID
26908595
Source
epmc
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
25
Issue
2
Publish Date
2016
Start Page
282
End Page
290
DOI
10.1158/1055-9965.epi-15-0847

The Glioma International Case-Control Study: A Report From the Genetic Epidemiology of Glioma International Consortium.

Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.

Authors
Amirian, ES; Armstrong, GN; Zhou, R; Lau, CC; Claus, EB; Barnholtz-Sloan, JS; Il'yasova, D; Schildkraut, J; Ali-Osman, F; Sadetzki, S; Johansen, C; Houlston, RS; Jenkins, RB; Lachance, D; Olson, SH; Bernstein, JL; Merrell, RT; Wrensch, MR; Davis, FG; Lai, R; Shete, S; Amos, CI; Scheurer, ME; Aldape, K; Alafuzoff, I; Brännström, T; Broholm, H; Collins, P; Giannini, C; Rosenblum, M; Tihan, T; Melin, BS; Bondy, ML
MLA Citation
Amirian, ES, Armstrong, GN, Zhou, R, Lau, CC, Claus, EB, Barnholtz-Sloan, JS, Il'yasova, D, Schildkraut, J, Ali-Osman, F, Sadetzki, S, Johansen, C, Houlston, RS, Jenkins, RB, Lachance, D, Olson, SH, Bernstein, JL, Merrell, RT, Wrensch, MR, Davis, FG, Lai, R, Shete, S, Amos, CI, Scheurer, ME, Aldape, K, Alafuzoff, I, Brännström, T, Broholm, H, Collins, P, Giannini, C, Rosenblum, M, Tihan, T, Melin, BS, and Bondy, ML. "The Glioma International Case-Control Study: A Report From the Genetic Epidemiology of Glioma International Consortium." American journal of epidemiology 183.2 (January 2016): 85-91.
PMID
26656478
Source
epmc
Published In
American Journal of Epidemiology
Volume
183
Issue
2
Publish Date
2016
Start Page
85
End Page
91
DOI
10.1093/aje/kwv235

Oxidative stress, oxidative balance score, and hypertension among a racially diverse population.

Hypertension is a risk factor for several vascular diseases. Evidence suggests that oxidative stress (OS) plays a significant role in its pathophysiology. Human studies have shown inconsistent results, varying based on the OS biomarker and study population. In a racially diverse population, examine the association between: (1) blood pressure or hypertension and four markers of OS and (2) blood pressure or hypertension and oxidative balance score (OBS). Using data (n = 317) from the cross-sectional study on race, stress, and hypertension, an OBS was constructed from various measures of pro-oxidant and antioxidant exposures. OS was assessed by four biomarkers: fluorescence oxidative products, F2-isoprostanes, mitochondrial DNA copy number, and gamma tocopherol. Multivariate linear and logistic regression analyses were used to estimate the associations of interest. None of the adjusted associations between hypertension and OS markers was statistically significant. OBS was inversely associated with hypertension after adjusting for study covariates. Persons with higher OBS have lower odds of having hypertension; however, the evidence on the relationship between OS markers and blood pressure remains unconvincing.

Authors
Annor, FB; Goodman, M; Okosun, IS; Wilmot, DW; Il'yasova, D; Ndirangu, M; Lakkur, S
MLA Citation
Annor, FB, Goodman, M, Okosun, IS, Wilmot, DW, Il'yasova, D, Ndirangu, M, and Lakkur, S. "Oxidative stress, oxidative balance score, and hypertension among a racially diverse population." Journal of the American Society of Hypertension : JASH 9.8 (August 2015): 592-599.
PMID
26160262
Source
epmc
Published In
Journal of the American Society of Hypertension
Volume
9
Issue
8
Publish Date
2015
Start Page
592
End Page
599
DOI
10.1016/j.jash.2015.05.014

A pooled multisite analysis of the effects of atopic medical conditions in glioma risk in different ethnic groups.

The incidences of atopic conditions (allergies, asthma, or eczema) and glioma vary by ethnicity. Atopic conditions are inversely associated with gliomas. We conducted a pooled multisite study investigating the associations of atopic conditions with glioma in different race/ethnicity groups.Using glioma cases and healthy controls, unconditional logistic regression was conducted to assess the associations of atopic conditions with glioma separately in white, black, Asian, and Hispanic subpopulations. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.Glioblastoma multiforme cases were less likely than controls to report a history of atopic conditions in whites (OR = 0.46, [95% CI, 0.38-0.54]) and Asians (OR = 0.27, [95% CI, 0.10-0.73]). The same trend was seen when looking at glioma cases of all histologies. An inverse association was not seen in blacks for glioblastoma multiforme or all histologies combined.The inverse association between glioma and atopic conditions may vary by ethnicity due to a difference in the biology of atopic conditions in different ethnicities but may be due to chance because of the limitations of small nonwhite sample sizes.

Authors
Krishnamachari, B; Il'yasova, D; Scheurer, ME; Bondy, M; Zhou, R; Wrensch, M; Davis, F
MLA Citation
Krishnamachari, B, Il'yasova, D, Scheurer, ME, Bondy, M, Zhou, R, Wrensch, M, and Davis, F. "A pooled multisite analysis of the effects of atopic medical conditions in glioma risk in different ethnic groups." Annals of epidemiology 25.4 (April 2015): 270-274.
PMID
25691445
Source
epmc
Published In
Annals of Epidemiology
Volume
25
Issue
4
Publish Date
2015
Start Page
270
End Page
274
DOI
10.1016/j.annepidem.2014.12.007

Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium.

Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.

Authors
Jalali, A; Amirian, ES; Bainbridge, MN; Armstrong, GN; Liu, Y; Tsavachidis, S; Jhangiani, SN; Plon, SE; Lau, CC; Claus, EB; Barnholtz-Sloan, JS; Il'yasova, D; Schildkraut, J; Ali-Osman, F; Sadetzki, S; Johansen, C; Houlston, RS; Jenkins, RB; Lachance, D; Olson, SH; Bernstein, JL; Merrell, RT; Wrensch, MR; Davis, FG; Lai, R; Shete, S; Aldape, K; Amos, CI; Muzny, DM; Gibbs, RA; Melin, BS; Bondy, ML
MLA Citation
Jalali, A, Amirian, ES, Bainbridge, MN, Armstrong, GN, Liu, Y, Tsavachidis, S, Jhangiani, SN, Plon, SE, Lau, CC, Claus, EB, Barnholtz-Sloan, JS, Il'yasova, D, Schildkraut, J, Ali-Osman, F, Sadetzki, S, Johansen, C, Houlston, RS, Jenkins, RB, Lachance, D, Olson, SH, Bernstein, JL, Merrell, RT, Wrensch, MR, Davis, FG, Lai, R, Shete, S, Aldape, K, Amos, CI, Muzny, DM, Gibbs, RA, Melin, BS, and Bondy, ML. "Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium." Scientific reports 5 (February 5, 2015): 8278-.
PMID
25652157
Source
epmc
Published In
Scientific Reports
Volume
5
Publish Date
2015
Start Page
8278
DOI
10.1038/srep08278

Germline mutations in shelterin complex genes are associated with familial glioma.

Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.

Authors
Bainbridge, MN; Armstrong, GN; Gramatges, MM; Bertuch, AA; Jhangiani, SN; Doddapaneni, H; Lewis, L; Tombrello, J; Tsavachidis, S; Liu, Y; Jalali, A; Plon, SE; Lau, CC; Parsons, DW; Claus, EB; Barnholtz-Sloan, J; Il'yasova, D; Schildkraut, J; Ali-Osman, F; Sadetzki, S; Johansen, C; Houlston, RS; Jenkins, RB; Lachance, D; Olson, SH; Bernstein, JL; Merrell, RT; Wrensch, MR; Walsh, KM; Davis, FG; Lai, R; Shete, S; Aldape, K; Amos, CI; Thompson, PA; Muzny, DM; Gibbs, RA; Melin, BS; Bondy, ML et al.
MLA Citation
Bainbridge, MN, Armstrong, GN, Gramatges, MM, Bertuch, AA, Jhangiani, SN, Doddapaneni, H, Lewis, L, Tombrello, J, Tsavachidis, S, Liu, Y, Jalali, A, Plon, SE, Lau, CC, Parsons, DW, Claus, EB, Barnholtz-Sloan, J, Il'yasova, D, Schildkraut, J, Ali-Osman, F, Sadetzki, S, Johansen, C, Houlston, RS, Jenkins, RB, Lachance, D, Olson, SH, Bernstein, JL, Merrell, RT, Wrensch, MR, Walsh, KM, Davis, FG, Lai, R, Shete, S, Aldape, K, Amos, CI, Thompson, PA, Muzny, DM, Gibbs, RA, Melin, BS, and Bondy, ML et al. "Germline mutations in shelterin complex genes are associated with familial glioma." Journal of the National Cancer Institute 107.1 (January 2015): 384-.
PMID
25482530
Source
epmc
Published In
Journal of the National Cancer Institute
Volume
107
Issue
1
Publish Date
2015
Start Page
384
DOI
10.1093/jnci/dju384

Urinary F2-isoprostanes and metabolic markers of fat oxidation.

Metabolomic studies of increased fat oxidation showed increase in circulating acylcarnitines C2, C8, C10, and C12 and decrease in C3, C4, and C5. We hypothesize that urinary F2-isoprostanes reflect intensity of fatty acid oxidation and are associated with circulating C2, C8, C10, and C12 directly and with C3, C4, and C5 inversely. Four urinary F2-isoprostane isomers and serum acylcarnitines are quantified using LC-MS/MS within the Insulin Resistance Atherosclerosis Study nondiabetic cohort (n = 682). Cross-sectional associations between fasting urinary F2-isoprostanes (summarized as a composite index) and the selected acylcarnitines are examined using generalized linear models. F2-isoprostane index is associated with C2 and C12 directly and with C5 inversely: the adjusted beta coefficients are 0.109, 0.072, and -0.094, respectively (P < 0.05). For these acylcarnitines and for F2-isoprostanes, the adjusted odds ratios (ORs) of incident diabetes are calculated from logistic regression models: the ORs (95% CI) are 0.77 (0.60-0.97), 0.79 (0.62-1.01), 1.18 (0.92-1.53), and 0.51 (0.35-0.76) for C2, C12, C5, and F2-isoprostanes, respectively. The direction of the associations between urinary F2-isoprostanes and three acylcarnitines (C2, C5, and C12) supports our hypothesis. The inverse associations of C2 and C12 and with incident diabetes are consistent with the suggested protective role of efficient fat oxidation.

Authors
Il'yasova, D; Wagenknecht, LE; Spasojevic, I; Watkins, S; Bowden, D; Wang, F; D'Agostino, RB
MLA Citation
Il'yasova, D, Wagenknecht, LE, Spasojevic, I, Watkins, S, Bowden, D, Wang, F, and D'Agostino, RB. "Urinary F2-isoprostanes and metabolic markers of fat oxidation." Oxidative medicine and cellular longevity 2015 (January 2015): 729191-.
PMID
25802683
Source
epmc
Published In
Oxidative Medicine and Cellular Longevity
Volume
2015
Publish Date
2015
Start Page
729191
DOI
10.1155/2015/729191

Donor-Specific Cell-Based Assays in Studying Sensitivity to Low-Dose Radiation: A Population-Based Perspective

Authors
Il’yasova, D; Kinev, A; Melton, CD; Davis, FG
MLA Citation
Il’yasova, D, Kinev, A, Melton, CD, and Davis, FG. "Donor-Specific Cell-Based Assays in Studying Sensitivity to Low-Dose Radiation: A Population-Based Perspective." Frontiers in Public Health 2 (November 18, 2014).
Source
crossref
Published In
Frontiers in Public Health
Volume
2
Publish Date
2014
DOI
10.3389/fpubh.2014.00244

Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer.

Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers.Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma.We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer.Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.

Authors
Andersson, U; Wibom, C; Cederquist, K; Aradottir, S; Borg, A; Armstrong, GN; Shete, S; Lau, CC; Bainbridge, MN; Claus, EB; Barnholtz-Sloan, J; Lai, R; Il'yasova, D; Houlston, RS; Schildkraut, J; Bernstein, JL; Olson, SH; Jenkins, RB; Lachance, DH; Wrensch, M; Davis, FG; Merrell, R; Johansen, C; Sadetzki, S; Gliogene Consortium, ; Bondy, ML; Melin, BS
MLA Citation
Andersson, U, Wibom, C, Cederquist, K, Aradottir, S, Borg, A, Armstrong, GN, Shete, S, Lau, CC, Bainbridge, MN, Claus, EB, Barnholtz-Sloan, J, Lai, R, Il'yasova, D, Houlston, RS, Schildkraut, J, Bernstein, JL, Olson, SH, Jenkins, RB, Lachance, DH, Wrensch, M, Davis, FG, Merrell, R, Johansen, C, Sadetzki, S, Gliogene Consortium, , Bondy, ML, and Melin, BS. "Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer." Neuro-oncology 16.10 (October 2014): 1333-1340.
PMID
24723567
Source
epmc
Published In
Neuro-Oncology
Volume
16
Issue
10
Publish Date
2014
Start Page
1333
End Page
1340
DOI
10.1093/neuonc/nou052

A pooled multisite analysis of the effects of female reproductive hormones on glioma risk.

The association between female reproductive factors and glioma risk is unclear, but most published studies have been limited by small sample size. We conducted a pooled multisite study of pre- and postmenopausal women, investigating the effect of female reproductive factors, including hormonal medications.Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (95 % CIs) assessing the effects of female reproductive factors and female hormonal medications in glioma cases and unrelated controls.Menarche over the age of 15 as compared to under 12 was associated with a statistically significant risk for glioma (OR 2.00, 95 % CI 1.47-2.71). Use of oral contraceptive pills (OCP) was inversely associated with risk of glioma (OR 0.61, 95 % CI 0.50-0.74), and there was an inverse trend with longer duration of OCP use (p for trend <0.0001). Use of hormone replacement therapy (HRT) was also inversely associated with risk of glioma (OR 0.55, 95 % CI 0.44-0.68), and there was an inverse trend with longer duration of use (p for trend <0.0001). Compared to those reporting neither OCP use nor HRT use, those who reported using both were less likely to have a diagnosis of glioma (OR 0.34, 95 % CI 0.24-0.48).Female reproductive hormones may decrease the risk for glioma. The association appears to be strongest with greater length of use and use of both HRT and OCP.

Authors
Krishnamachari, B; Il'yasova, D; Scheurer, ME; Bondy, ML; Wrensch, M; Davis, FG
MLA Citation
Krishnamachari, B, Il'yasova, D, Scheurer, ME, Bondy, ML, Wrensch, M, and Davis, FG. "A pooled multisite analysis of the effects of female reproductive hormones on glioma risk." Cancer causes & control : CCC 25.8 (August 2014): 1007-1013.
PMID
24890803
Source
epmc
Published In
Cancer Causes & Control
Volume
25
Issue
8
Publish Date
2014
Start Page
1007
End Page
1013
DOI
10.1007/s10552-014-0400-8

Exploring the association between melanoma and glioma risks.

Gliomas are one of the most fatal malignancies, with largely unknown etiology. This study examines a possible connection between glioma and melanoma, which might provide insight into gliomas' etiology.Using data provided by the Surveillance, Epidemiology, and End Results program from 1992 to 2009, a cohort was constructed to determine the incidence rates of glioma among those who had a prior diagnosis of invasive melanoma. Glioma rates in those with prior melanoma were compared with those in the general population.The incidence rate of all gliomas was greater among melanoma cases than in the general population: 10.46 versus 6.13 cases per 100,000 person-years, standardized incidence ratios = 1.42 (1.22-1.62). The female excess rate was slightly greater (42%) than that among males (29%). Sensitivity analyses did not reveal evidence that radiation treatment of melanoma is responsible for the detected gap in the rates of gliomas.Our analysis documented increased risk of glioma among melanoma patients. Because no common environmental risk factors are identified for glioma and melanoma, it is hypothesized that a common genetic predisposition may be responsible for the detected association.

Authors
Scarbrough, PM; Akushevich, I; Wrensch, M; Il'yasova, D
MLA Citation
Scarbrough, PM, Akushevich, I, Wrensch, M, and Il'yasova, D. "Exploring the association between melanoma and glioma risks." Annals of epidemiology 24.6 (June 2014): 469-474.
Website
http://hdl.handle.net/10161/14830
PMID
24703682
Source
epmc
Published In
Annals of Epidemiology
Volume
24
Issue
6
Publish Date
2014
Start Page
469
End Page
474
DOI
10.1016/j.annepidem.2014.02.010

Exploring the association between melanoma and glioma risks

Purpose: Gliomas are one of the most fatal malignancies, with largely unknown etiology. This study examines a possible connection between glioma and melanoma, which might provide insight into gliomas' etiology. Methods: Using data provided by the Surveillance, Epidemiology, and End Results program from 1992 to 2009, a cohort was constructed to determine the incidence rates of glioma among those who had a prior diagnosis of invasive melanoma. Glioma rates in those with prior melanoma were compared with those in the general population. Results: The incidence rate of all gliomas was greater among melanoma cases than in the general population: 10.46 versus 6.13 cases per 100,000 person-years, standardized incidence ratios = 1.42 (1.22-1.62). The female excess rate was slightly greater (42%) than that among males (29%). Sensitivity analyses did not reveal evidence that radiation treatment of melanoma is responsible for the detected gap in the rates of gliomas. Conclusions: Our analysis documented increased risk of glioma among melanoma patients. Because no common environmental risk factors are identified for glioma and melanoma, it is hypothesized that a common genetic predisposition may be responsible for the detected association. © 2014 Elsevier Inc.

Authors
Scarbrough, PM; Akushevich, I; Wrensch, M; Il'yasova, D
MLA Citation
Scarbrough, PM, Akushevich, I, Wrensch, M, and Il'yasova, D. "Exploring the association between melanoma and glioma risks." Annals of Epidemiology 24.6 (2014): 469-474.
Source
scival
Published In
Annals of Epidemiology
Volume
24
Issue
6
Publish Date
2014
Start Page
469
End Page
474
DOI
10.1016/j.annepidem.2014.02.010

Endothelial colony forming cells (ECFCs) as a model for studying effects of low-dose ionizing radiation: growth inhibition by a single dose.

Identification of measurable nontransient responses to low-dose radiation in human primary cell cultures remains a problem. To this end, circulating endothelial colony-forming (progenitor) cells (ECFCs) were examined as an experimental model. ECFCs were isolated from three cord blood donors. Cells were positive for endothelial cell markers and remained highly proliferative after long-term cryopreservation. A single dose of X-ray radiation (0.06-0.38 Gy) inhibited ECFC culture growth. This effect was evident at 48 hours and persisted up to 72 hr postirradiation. Such protracted cytostatic response of ECFCs to low-dose radiation suggests that ECFC primary cultures can be used to study low-dose radiation effects.

Authors
Kinev, AV; Levering, V; Young, K; Ali-Osman, F; Truskey, GA; Dewhirst, MW; Il'yasova, D
MLA Citation
Kinev, AV, Levering, V, Young, K, Ali-Osman, F, Truskey, GA, Dewhirst, MW, and Il'yasova, D. "Endothelial colony forming cells (ECFCs) as a model for studying effects of low-dose ionizing radiation: growth inhibition by a single dose." Cancer Invest 31.5 (June 2013): 359-364.
PMID
23621632
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
31
Issue
5
Publish Date
2013
Start Page
359
End Page
364
DOI
10.3109/07357907.2013.789903

Description of selected characteristics of familial glioma patients - Results from the Gliogene Consortium

Background: While certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained from 14 centres in the United States (US), Europe and Israel as part of the Gliogene Consortium. Methods: Families with 2 or more verified gliomas were recruited between January 2007 and February 2011. Distributions of demographic characteristics and clinical variables of gliomas in the families were described based on information derived from personal questionnaires. Findings: The study population comprised 841 glioma patients identified in 376 families (9797 individuals). There were more cases of glioma among males, with a male to female ratio of 1.25. In most families (83%), 2 gliomas were reported, with 3 and 4 gliomas in 13% and 3% of the families, respectively. For families with 2 gliomas, 57% were among 1st-degree relatives, and 31.5% among 2nd-degree relatives. Overall, the mean (±standard deviation [SD]) diagnosis age was 49.4 (± 18.7) years. In 48% of families with 2 gliomas, at least one was diagnosed at <40 y, and in 12% both were diagnosed under 40 y of age. Most of these families (76%) had at least one grade IV glioblastoma multiforme (GBM), and in 32% both cases were grade IV gliomas. The most common glioma subtype was GBM (55%), followed by anaplastic astrocytoma (10%) and oligodendroglioma (8%). Individuals with grades I-II were on average 17 y younger than those with grades III-IV. Interpretation: Familial glioma cases are similar to sporadic cases in terms of gender distribution, age, morphology and grade. Most familial gliomas appear to comprise clusters of two cases suggesting low penetrance, and that the risk of developing additional gliomas is probably low. These results should be useful in the counselling and clinical management of individuals with a family history of glioma. © 2012 Elsevier Ltd.

Authors
Sadetzki, S; Bruchim, R; Oberman, B; Armstrong, GN; Lau, CC; Claus, EB; Barnholtz-Sloan, JS; Il'yasova, D; Schildkraut, J; Johansen, C; al, E
MLA Citation
Sadetzki, S, Bruchim, R, Oberman, B, Armstrong, GN, Lau, CC, Claus, EB, Barnholtz-Sloan, JS, Il'yasova, D, Schildkraut, J, Johansen, C, and al, E. "Description of selected characteristics of familial glioma patients - Results from the Gliogene Consortium." European Journal of Cancer (2013).
PMID
23290425
Source
scival
Published In
European Journal of Cancer
Publish Date
2013
DOI
10.1016/j.ejca.2012.11.009

Description of selected characteristics of familial glioma patients-Results from the Gliogene Consortium

Background: While certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained from 14 centres in the United States (US), Europe and Israel as part of the Gliogene Consortium. Methods: Families with 2 or more verified gliomas were recruited between January 2007 and February 2011. Distributions of demographic characteristics and clinical variables of gliomas in the families were described based on information derived from personal questionnaires. Findings: The study population comprised 841 glioma patients identified in 376 families (9797 individuals). There were more cases of glioma among males, with a male to female ratio of 1.25. In most families (83%), 2 gliomas were reported, with 3 and 4 gliomas in 13% and 3% of the families, respectively. For families with 2 gliomas, 57% were among 1st-degree relatives, and 31.5% among 2nd-degree relatives. Overall, the mean (±standard deviation [SD]) diagnosis age was 49.4 (± 18.7) years. In 48% of families with 2 gliomas, at least one was diagnosed at <40 y, and in 12% both were diagnosed under 40 y of age. Most of these families (76%) had at least one grade IV glioblastoma multiforme (GBM), and in 32% both cases were grade IV gliomas. The most common glioma subtype was GBM (55%), followed by anaplastic astrocytoma (10%) and oligodendroglioma (8%). Individuals with grades I-II were on average 17 y younger than those with grades III-IV. Interpretation: Familial glioma cases are similar to sporadic cases in terms of gender distribution, age, morphology and grade. Most familial gliomas appear to comprise clusters of two cases suggesting low penetrance, and that the risk of developing additional gliomas is probably low. These results should be useful in the counselling and clinical management of individuals with a family history of glioma. © 2012 Elsevier Ltd. All rights reserved.

Authors
Sadetzki, S; Bruchim, R; Oberman, B; Armstrong, GN; Lau, CC; Claus, EB; Barnholtz-Sloan, JS; Il'Yasova, D; Schildkraut, J; Johansen, C; Houlston, RS; Shete, S; Amos, CI; Bernstein, JL; Olson, SH; Jenkins, RB; Lachance, D; Vick, NA; Merrell, R; Wrensch, M; Davis, FG; McCarthy, BJ; Lai, R; Melin, BS; Bondy, ML
MLA Citation
Sadetzki, S, Bruchim, R, Oberman, B, Armstrong, GN, Lau, CC, Claus, EB, Barnholtz-Sloan, JS, Il'Yasova, D, Schildkraut, J, Johansen, C, Houlston, RS, Shete, S, Amos, CI, Bernstein, JL, Olson, SH, Jenkins, RB, Lachance, D, Vick, NA, Merrell, R, Wrensch, M, Davis, FG, McCarthy, BJ, Lai, R, Melin, BS, and Bondy, ML. "Description of selected characteristics of familial glioma patients-Results from the Gliogene Consortium." European Journal of Cancer 49.6 (2013): 1335-1345.
Source
scival
Published In
European Journal of Cancer
Volume
49
Issue
6
Publish Date
2013
Start Page
1335
End Page
1345
DOI
10.1016/j.ejca.2012.11.009

Systemic oxidative stress, as measured by urinary allantoin and F(2)-isoprostanes, is not increased in Down syndrome.

PURPOSE: Oxidative stress has been implicated in Down syndrome (DS) pathology. This study compares DS individuals and controls on their urinary levels of allantoin and 2,3-dinor-iPF2α-III; these biomarkers have been previously validated in a clinical model of oxidative stress. METHODS: Urine samples were collected from 48 individuals with DS and 130 controls. Biomarkers were assayed by ultraperformance liquid chromatography-tandem mass spectrometry, normalized by urinary creatinine concentration. RESULTS: After adjusting for age and gender, mean allantoin levels were lower among DS individuals versus controls (P = .04). The adjusted mean levels of 2,3-dinor-iPF2α-III were similar in DS individuals and controls (P = .7). CONCLUSIONS: Our results do not support the hypothesis that DS individuals have chronic systemic oxidative stress.

Authors
Tolun, AA; Scarbrough, PM; Zhang, H; McKillop, J-A; Wang, F; Kishnani, PS; Millington, DS; Young, SP; Il'yasova, D
MLA Citation
Tolun, AA, Scarbrough, PM, Zhang, H, McKillop, J-A, Wang, F, Kishnani, PS, Millington, DS, Young, SP, and Il'yasova, D. "Systemic oxidative stress, as measured by urinary allantoin and F(2)-isoprostanes, is not increased in Down syndrome." Ann Epidemiol 22.12 (December 2012): 892-894.
PMID
23063134
Source
pubmed
Published In
Annals of Epidemiology
Volume
22
Issue
12
Publish Date
2012
Start Page
892
End Page
894
DOI
10.1016/j.annepidem.2012.09.005

Urinary biomarkers of oxidative status.

Oxidative damage produced by reactive oxygen species (ROS) has been implicated in the etiology and pathology of many health conditions, including a large number of chronic diseases. Urinary biomarkers of oxidative status present a great opportunity to study redox balance in human populations. With urinary biomarkers, specimen collection is non-invasive and the organic/metal content is low, which minimizes the artifactual formation of oxidative damage to molecules in specimens. Also, urinary levels of the biomarkers present intergraded indices of redox balance over a longer period of time compared to blood levels. This review summarizes the criteria for evaluation of biomarkers applicable to epidemiological studies and evaluation of several classes of biomarkers that are formed non-enzymatically: oxidative damage to lipids, proteins, DNA, and allantoin, an oxidative product of uric acid. The review considers formation, metabolism, and exertion of each biomarker, available data on validation in animal and clinical models of oxidative stress, analytical approaches, and their intra- and inter-individual variation. The recommended biomarkers for monitoring oxidative status over time are F₂-isoprostanes and 8-oxodG. For inter-individual comparisons, F₂-isoprostanes are recommended, whereas urinary 8-oxodG levels may be confounded by differences in the DNA repair capacity. Promising urinary biomarkers include allantoin, acrolein-lysine, and dityrosine.

Authors
Il'yasova, D; Scarbrough, P; Spasojevic, I
MLA Citation
Il'yasova, D, Scarbrough, P, and Spasojevic, I. "Urinary biomarkers of oxidative status." Clin Chim Acta 413.19-20 (October 9, 2012): 1446-1453. (Review)
PMID
22683781
Source
pubmed
Published In
Clinica Chimica Acta
Volume
413
Issue
19-20
Publish Date
2012
Start Page
1446
End Page
1453
DOI
10.1016/j.cca.2012.06.012

Racial differences in urinary F2-isoprostane levels and the cross-sectional association with BMI.

Levels of four urinary F(2)-isoprostanes (F(2)-IsoPs) were examined in a large sample of the Insulin Resistance Atherosclerosis Study (IRAS) multiethnic cohort: 237 African Americans (AAs), 342 non-Hispanic whites (NHWs), and 275 Hispanic whites (HWs). F(2)-IsoP isomers - iPF2a-III, 2,3-dinor-iPF2a-III, iPF2a-VI, and 8,12-iso-iPF2a-VI - were measured in 854 urine samples using liquid chromatography with tandem mass spectrometry detection. In AAs, levels of all four F(2)-IsoPs were lower compared with NHWs and HWs (P values <0.05). When stratified by BMI, this gap was not observed among participants with normal BMI but appeared among overweight participants and increased among obese participants. Examining the slopes of the associations between BMI and F(2)-IsoPs showed no association between these variables among AAs (P values >0.2), and positive associations among whites (P values <0.05). Taking into account that positive cross-sectional associations between systemic F(2)-IsoP levels and BMI have been consistently demonstrated in many study populations, the lack of such an association among AAs reveals a new facet of racial/ethnic differences in obesity-related risk profiles.

Authors
Il'yasova, D; Wang, F; Spasojevic, I; Base, K; D'Agostino, RB; Wagenknecht, LE
MLA Citation
Il'yasova, D, Wang, F, Spasojevic, I, Base, K, D'Agostino, RB, and Wagenknecht, LE. "Racial differences in urinary F2-isoprostane levels and the cross-sectional association with BMI." Obesity (Silver Spring) 20.10 (October 2012): 2147-2150.
PMID
22836686
Source
pubmed
Published In
Obesity
Volume
20
Issue
10
Publish Date
2012
Start Page
2147
End Page
2150
DOI
10.1038/oby.2012.170

Urinary F2-isoprostanes, obesity, and weight gain in the IRAS cohort.

Obesity has been associated with increased F(2)-isoprostane (F(2)-IsoP) levels cross-sectionally. However, the prospective association may be inverse, based on our earlier finding that elevated urinary F(2)-IsoP levels predict lower risk of diabetes. This earlier finding led us to hypothesize that urinary F(2)-IsoPs reflect the intensity of oxidative metabolism and as such predict lower risk of both diabetes and weight gain. We examined cross-sectional relationships with obesity and prospective relationships with weight gain using the data from 299 participants of the Insulin Resistance Atherosclerosis Study (IRAS), all of whom were free of diabetes at baseline. Four urinary F(2)-IsoPs were assayed in stored baseline urine samples using liquid chromatography with tandem mass spectrometry: iPF(2α)-III, 2,3-dinor-iPF(2α)-III, iPF(2α)-VI, and 8,12-iso-iPF(2α)-VI (F(2)-IsoP 1-4, respectively). Baseline F(2)-IsoPs were positively associated with baseline measures of obesity; the strongest associations were found with two F(2)-IsoPs: odds ratios (95% confidence intervals) for overall and abdominal obesity were 1.74 (1.26-2.40) and 1.63 (1.18-2.24) for F(2)-IsoP2 and 1.47 (1.12-1.94) and 1.64 (1.22-2.20) for F(2)-IsoP4. F(2)-IsoP2 showed the strongest and significant inverse association with weight gain during the 5-year follow-up period: increase in F(2)-IsoP2 equal to 1 s.d. was associated with 0.90 kg lower weight gain (P = 0.02) and the odds ratios for relative (≥5%) and absolute (≥5 kg) weight gain were 0.67 (0.47-0.96) and 0.57 (0.37-0.87), respectively. The other three F(2)-IsoPs were consistently inversely associated with weight gain, although not significantly, suggesting that different F(2)-IsoPs vary in their ability to detect the association with weight gain.

Authors
Il'yasova, D; Wang, F; Spasojevic, I; Base, K; D'Agostino, RB; Wagenknecht, LE
MLA Citation
Il'yasova, D, Wang, F, Spasojevic, I, Base, K, D'Agostino, RB, and Wagenknecht, LE. "Urinary F2-isoprostanes, obesity, and weight gain in the IRAS cohort." Obesity (Silver Spring) 20.9 (September 2012): 1915-1921.
PMID
21959342
Source
pubmed
Published In
Obesity
Volume
20
Issue
9
Publish Date
2012
Start Page
1915
End Page
1921
DOI
10.1038/oby.2011.292

Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma.

The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P(trend) <1.0 × 10(-8)). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.

Authors
Liu, Y; Melin, BS; Rajaraman, P; Wang, Z; Linet, M; Shete, S; Amos, CI; Lau, CC; Scheurer, ME; Tsavachidis, S; Armstrong, GN; Houlston, RS; Hosking, FJ; Claus, EB; Barnholtz-Sloan, J; Lai, R; Il'yasova, D; Schildkraut, J; Sadetzki, S; Johansen, C; Bernstein, JL; Olson, SH; Jenkins, RB; LaChance, D; Vick, NA; Wrensch, M; Davis, F; McCarthy, BJ; Andersson, U; Thompson, PA; Chanock, S; Gliogene Consortium, ; Bondy, ML
MLA Citation
Liu, Y, Melin, BS, Rajaraman, P, Wang, Z, Linet, M, Shete, S, Amos, CI, Lau, CC, Scheurer, ME, Tsavachidis, S, Armstrong, GN, Houlston, RS, Hosking, FJ, Claus, EB, Barnholtz-Sloan, J, Lai, R, Il'yasova, D, Schildkraut, J, Sadetzki, S, Johansen, C, Bernstein, JL, Olson, SH, Jenkins, RB, LaChance, D, Vick, NA, Wrensch, M, Davis, F, McCarthy, BJ, Andersson, U, Thompson, PA, Chanock, S, Gliogene Consortium, , and Bondy, ML. "Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma." Hum Genet 131.9 (September 2012): 1507-1517.
PMID
22688887
Source
pubmed
Published In
Human Genetics
Volume
131
Issue
9
Publish Date
2012
Start Page
1507
End Page
1517
DOI
10.1007/s00439-012-1187-x

Systemic markers of oxidative status and colorectal adenomatous polyps.

PURPOSE: Oxidative damage has been implicated in carcinogenesis. We hypothesized that elevated systemic oxidative status would be associated with later occurrence of colorectal adenomatous polyps, a precursor of colorectal cancer. METHODS: We examined the prospective association between four systemic markers of oxidative status and colorectal adenomatous polyps within a nondiabetic subcohort of the Insulin Resistance Atherosclerosis Study (n = 425). Urine samples were collected from 1992 to 1994 and colorectal adenomas prevalence were assessed in 2002 to 2004. Oxidative status markers were assessed, which included four F(2)-isoprostanes (F(2)-IsoPs) from the classes III and IV: iPF2α-III, 2,3-dinor-iPF2α-III (a metabolite of iPF2α-III), iPF2α-VI, and 8,12-iso-iPF2α-VI. All biomarkers were quantified using liquid chromatography-tandem mass spectrometry. Prospective associations were assessed using multivariate logistic regression analysis. RESULTS: The adjusted odds ratio (OR) (95% confidence interval [CI]) for occurrence of colorectal adenomatous polyps and scaled to 1 SD of F(2)-IsoP distribution were 1.16 (95% CI, 0.88-1.50), 0.88 (95% CI, 0.63-1.17), 1.04 (95% CI, 0.80-1.34), and 1.16 (95% CI, 0.90-1.48) for iPF2α-III, iPF2α-VI, 8,12-iso-iPF2α-VI, and 2,3-dinor-iPF2α-III, respectively. CONCLUSIONS: The lack of association between F(2)-IsoPs and adenomatous polyps does not support the hypothesis that elevated oxidative status is associated with colorectal adenomatous polyp occurrence during a 10-year period of follow-up.

Authors
Siamakpour-Reihani, S; Scarbrough, PM; Wang, F; Spasojevic, I; Base, K; Sedjo, R; D'Agostino, RB; Il'yasova, D
MLA Citation
Siamakpour-Reihani, S, Scarbrough, PM, Wang, F, Spasojevic, I, Base, K, Sedjo, R, D'Agostino, RB, and Il'yasova, D. "Systemic markers of oxidative status and colorectal adenomatous polyps." Ann Epidemiol 22.8 (August 2012): 587-591.
PMID
22695388
Source
pubmed
Published In
Annals of Epidemiology
Volume
22
Issue
8
Publish Date
2012
Start Page
587
End Page
591
DOI
10.1016/j.annepidem.2012.05.001

Increase in circulating levels of IGF-1 and IGF-1/IGFBP-3 molar ratio over a decade is associated with colorectal adenomatous polyps.

High levels of circulating insulin-like growth factor-1 (IGF-1) have been associated with increased risk of several cancers. Regarding colorectal cancer, these associations are generally weak. We hypothesized that an increase in IGF-1 over time would be a stronger risk factor for cancer-related outcomes than the actual levels. In this analysis we utilized existing data from the Insulin Resistance and Atherosclerosis Study (IRAS). Circulating IGF-1 levels and molar ratios of IGF-1 to IGF binding protein 3 (IGFBP-3) were measured at three time points, within a 10-year follow-up period. We examined the associations of increase of the two variables with the presence of colorectal adenoma at the end of follow-up among participants with normal glucose tolerance at baseline. This included 143 individuals, from which 24 were diagnosed with adenomatous polyps. Although the mean levels of IGF-1 and IGF-1/IGFBP-3 decline with age, ~ 30% of the participants showed an increase of at least fifteen percent ("ever increase") in one or both of these variables, compared to baseline. We found a positive association between "ever increase" in IGF-1 or IGF-1/IGFBP-3 and the presence of colorectal adenoma: ORs were 3.81 (95% CI: 1.30-10.8) and 2.83 (95% CI: 1.00-8.22), respectively. No association was found when analyzing the actual levels of both variables at any time point. Our data suggest that an increase in circulating IGF-1 or IGF-1/IGFBP-3 may represent a disturbed GH/IGF1 homeostasis, which could favor the development of precancerous lesions such as colorectal adenoma.

Authors
Soubry, A; Il'yasova, D; Sedjo, R; Wang, F; Byers, T; Rosen, C; Yashin, A; Ukraintseva, S; Haffner, S; D'Agostino, R
MLA Citation
Soubry, A, Il'yasova, D, Sedjo, R, Wang, F, Byers, T, Rosen, C, Yashin, A, Ukraintseva, S, Haffner, S, and D'Agostino, R. "Increase in circulating levels of IGF-1 and IGF-1/IGFBP-3 molar ratio over a decade is associated with colorectal adenomatous polyps." International journal of cancer 131.2 (July 2012): 512-517.
Website
http://hdl.handle.net/10161/14914
PMID
21898383
Source
epmc
Published In
International Journal of Cancer
Volume
131
Issue
2
Publish Date
2012
Start Page
512
End Page
517
DOI
10.1002/ijc.26393

Urinary F2-isoprostanes as a biomarker of reduced risk of type 2 diabetes.

OBJECTIVE: We have previously reported evidence of an inverse association between a urinary F(2)-isoprostane and type 2 diabetes risk in a pilot case-control study nested within the Insulin Resistance Atherosclerosis Study (IRAS). Here, we report the results from the study extended to the entire IRAS cohort. RESEARCH DESIGN AND METHODS: This prospective study included 138 incident type 2 diabetes case and 714 noncase subjects. Four F(2)-isoprostanes (iPF2α-III; 2,3-dinor-iPF2α-III; iPF2α-VI; and 8,12-iso-iPF2α-VI) were assayed in baseline urine samples using liquid chromatography-tandem mass spectrometry. RESULTS: Three F(2)-isoprostanes showed significant inverse associations with type 2 diabetes risk: the adjusted odds ratios were 0.52 (95% CI 0.39-0.67), 0.56 (0.42-0.73), 0.62 (0.48-0.79), and 0.91 (0.72-1.12) for iPF2α-III; 2,3-dinor-iPF2α-III; iPF2α-VI; and 8,12-iso-iPF2α-VI, respectively. CONCLUSIONS: Our findings indicate that urinary F(2)-isoprostanes are inversely associated with type 2 diabetes risk beyond the traditional risk factors and may be useful in identifying high-risk populations.

Authors
Il'yasova, D; Spasojevic, I; Base, K; Zhang, H; Wang, F; Young, SP; Millington, DS; D'Agostino, RB; Wagenknecht, LE
MLA Citation
Il'yasova, D, Spasojevic, I, Base, K, Zhang, H, Wang, F, Young, SP, Millington, DS, D'Agostino, RB, and Wagenknecht, LE. "Urinary F2-isoprostanes as a biomarker of reduced risk of type 2 diabetes." Diabetes Care 35.1 (January 2012): 173-174.
PMID
22100959
Source
pubmed
Published In
Diabetes Care
Volume
35
Issue
1
Publish Date
2012
Start Page
173
End Page
174
DOI
10.2337/dc11-1502

A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma

Background: We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma. Methods: First, we fit segregation models by formulating the likelihood for a person to have a bivariate phenotype, affection status and age of onset, along with other covariates, and from these we estimate population trait allele frequencies and penetrance parameters as a function of age (N = 281 multiplex glioma pedigrees). Second, the best fitting models are used as trait models in multipoint linkage analysis (N = 74 informative multiplex glioma pedigrees). To correct for ascertainment, a prevalence constraint is used in the likelihood of the segregation models for all 281 pedigrees. Then the trait allele frequencies are reestimated for the pedigree founders of the subset of 74 pedigrees chosen for linkage analysis. Results: Using the best-fitting segregation models in model-based multipoint linkage analysis, we identified 2 separate peaks on chromosome 17; the first agreed with a region identified by Shete and colleagues who used model-free affected-only linkage analysis, but with a narrowed peak: and the second agreed with a second region they found but had a larger maximum log of the odds (LOD). Conclusions: Our approach was able to narrow the linkage peak previously published for glioma. Impact: We provide a practical solution to model-based linkage analysis for disease affection status with variable age of onset for the kinds of pedigree data often collected for linkage analysis. ©2012 AACR.

Authors
Sun, X; Vengoechea, J; Elston, R; Chen, Y; Amos, CI; Armstrong, G; Bernstein, JL; Claus, E; Davis, F; Houlston, RS; Il'yasova, D; Jenkins, RB; Johansen, C; Lai, R; Lau, CC; Liu, Y; McCarthy, BJ; Olson, SH; Sadetzki, S; Schildkraut, J; Shete, S; Yu, R; Vick, NA; Merrell, R; Wrensch, M; Yang, P; Melin, B; Bondy, ML; Barnholtz-Sloan, JS
MLA Citation
Sun, X, Vengoechea, J, Elston, R, Chen, Y, Amos, CI, Armstrong, G, Bernstein, JL, Claus, E, Davis, F, Houlston, RS, Il'yasova, D, Jenkins, RB, Johansen, C, Lai, R, Lau, CC, Liu, Y, McCarthy, BJ, Olson, SH, Sadetzki, S, Schildkraut, J, Shete, S, Yu, R, Vick, NA, Merrell, R, Wrensch, M, Yang, P, Melin, B, Bondy, ML, and Barnholtz-Sloan, JS. "A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma." Cancer Epidemiology Biomarkers and Prevention 21.12 (2012): 2242-2251.
PMID
22962404
Source
scival
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
21
Issue
12
Publish Date
2012
Start Page
2242
End Page
2251
DOI
10.1158/1055-9965.EPI-12-0703

Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium.

Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma.

Authors
Shete, S; Lau, CC; Houlston, RS; Claus, EB; Barnholtz-Sloan, J; Lai, R; Il'yasova, D; Schildkraut, J; Sadetzki, S; Johansen, C; Bernstein, JL; Olson, SH; Jenkins, RB; Yang, P; Vick, NA; Wrensch, M; Davis, FG; McCarthy, BJ; Leung, EH-C; Davis, C; Cheng, R; Hosking, FJ; Armstrong, GN; Liu, Y; Yu, RK; Henriksson, R; Gliogene Consortium, ; Melin, BS; Bondy, ML
MLA Citation
Shete, S, Lau, CC, Houlston, RS, Claus, EB, Barnholtz-Sloan, J, Lai, R, Il'yasova, D, Schildkraut, J, Sadetzki, S, Johansen, C, Bernstein, JL, Olson, SH, Jenkins, RB, Yang, P, Vick, NA, Wrensch, M, Davis, FG, McCarthy, BJ, Leung, EH-C, Davis, C, Cheng, R, Hosking, FJ, Armstrong, GN, Liu, Y, Yu, RK, Henriksson, R, Gliogene Consortium, , Melin, BS, and Bondy, ML. "Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium." Cancer Res 71.24 (December 15, 2011): 7568-7575.
PMID
22037877
Source
pubmed
Published In
Cancer Research
Volume
71
Issue
24
Publish Date
2011
Start Page
7568
End Page
7575
DOI
10.1158/0008-5472.CAN-11-0013

What can we learn from the age- and race/ethnicity- specific rates of inflammatory breast carcinoma?

Inflammatory Breast Carcinoma (IBC), the most aggressive type of breast tumor with unique clinicopathological presentation, is hypothesized to have distinct etiology with a socioeconomic status (SES) component. Using the Surveillance, Epidemiology and End Results (SEER) Program data for 2004-2007, we compare incidence rates of IBC to non-inflammatory locally advanced breast cancer (LABC) among racial/ethnic groups with different SES. The analysis includes women 20-84 years of age. To examine evidence for the distinct etiology of IBC, we analyzed age-distribution patterns of IBC and non-inflammatory LABC, using a mathematical carcinogenesis model. Based on the Collaborative Staging Extension codes, 2,942 incident IBC cases (codes 71 and 73) and 5,721 non-inflammatory LABC cases (codes 40-62) were identified during the four-year study period. Age-adjusted rates of IBC among non-Hispanic White and Hispanic women were similar (2.5/100,000 in both groups). Similar rates were also found in non-inflammatory LABC in these two groups (4.8/100,000 and 4.2/100,000, respectively). In African-American women, the IBC (3.91/100,000) and non-inflammatory LABC (8.47/100,000) rates were greater compared with other ethnic/racial sub-groups. However, the ratio of rates of IBC/non-inflammatory LABC was similar among all the racial/ethnic groups, suggesting that African-American women are susceptible to aggressive breast tumors in general but not specifically to IBC. The mathematical model successfully predicted the observed age-specific rates of both examined breast tumors and revealed distinct patterns. IBC rates increased until age 65 and then slightly decreased, whereas non-inflammatory LABC rates steadily increased throughout the entire age interval. The number of critical transition carcinogenesis stages (m-stages) predicted by the model were 6.3 and 8.5 for IBC and non-inflammatory LABC, respectively, supporting different etiologies of these breast tumors.

Authors
Il'yasova, D; Siamakpour-Reihani, S; Akushevich, I; Akushevich, L; Spector, N; Schildkraut, J
MLA Citation
Il'yasova, D, Siamakpour-Reihani, S, Akushevich, I, Akushevich, L, Spector, N, and Schildkraut, J. "What can we learn from the age- and race/ethnicity- specific rates of inflammatory breast carcinoma?." Breast cancer research and treatment 130.2 (November 2011): 691-697.
PMID
21850396
Source
epmc
Published In
Breast Cancer Research and Treatment
Volume
130
Issue
2
Publish Date
2011
Start Page
691
End Page
697
DOI
10.1007/s10549-011-1719-4

Associations of high-grade glioma with glioma risk alleles and histories of allergy and smoking.

Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility. Data from 855 high-grade glioma cases and 1,160 controls from 4 geographic regions of the United States during 1997-2008 were analyzed for interactions between allergy and smoking histories and inherited variants in 5 established glioma risk regions: 5p15.3 (TERT), 8q24.21 (CCDC26/MLZE), 9p21.3 (CDKN2B), 11q23.3 (PHLDB1/DDX6), and 20q13.3 (RTEL1). The inverse relation between allergy and glioma was stronger among those who did not (odds ratio(allergy-glioma) = 0.40, 95% confidence interval: 0.28, 0.58) versus those who did (odds ratio(allergy-glioma) = 0.76, 95% confidence interval: 0.59, 0.97; P(interaction) = 0.02) carry the 9p21.3 risk allele. However, the inverse association with allergy was stronger among those who carried (odds ratio(allergy-glioma) = 0.44, 95% confidence interval: 0.29, 0.68) versus those who did not carry (odds ratio(allergy-glioma) = 0.68, 95% confidence interval: 0.54, 0.86) the 20q13.3 glioma risk allele, but this interaction was not statistically significant (P = 0.14). No relation was observed between glioma risk and smoking (odds ratio = 0.92, 95% confidence interval: 0.77, 1.10; P = 0.37), and there were no interactions for glioma risk of smoking history with any of the risk alleles. The authors' observations are consistent with a recent report that the inherited glioma risk variants in chromosome regions 9p21.3 and 20q13.3 may modify the inverse association of allergy and glioma.

Authors
Lachance, DH; Yang, P; Johnson, DR; Decker, PA; Kollmeyer, TM; McCoy, LS; Rice, T; Xiao, Y; Ali-Osman, F; Wang, F; Stoddard, SM; Sprau, DJ; Kosel, ML; Wiencke, JK; Wiemels, JL; Patoka, JS; Davis, F; McCarthy, B; Rynearson, AL; Worra, JB; Fridley, BL; O'Neill, BP; Buckner, JC; Il'yasova, D; Jenkins, RB; Wrensch, MR
MLA Citation
Lachance, DH, Yang, P, Johnson, DR, Decker, PA, Kollmeyer, TM, McCoy, LS, Rice, T, Xiao, Y, Ali-Osman, F, Wang, F, Stoddard, SM, Sprau, DJ, Kosel, ML, Wiencke, JK, Wiemels, JL, Patoka, JS, Davis, F, McCarthy, B, Rynearson, AL, Worra, JB, Fridley, BL, O'Neill, BP, Buckner, JC, Il'yasova, D, Jenkins, RB, and Wrensch, MR. "Associations of high-grade glioma with glioma risk alleles and histories of allergy and smoking." Am J Epidemiol 174.5 (September 1, 2011): 574-581.
PMID
21742680
Source
pubmed
Published In
American Journal of Epidemiology
Volume
174
Issue
5
Publish Date
2011
Start Page
574
End Page
581
DOI
10.1093/aje/kwr124

Medical diagnostic radiation exposures and risk of gliomas.

High-dose ionizing radiation is an established risk factor for glioma, but it remains unknown whether moderate- and low-dose radiation increase glioma risk. In this analysis, we assessed the evidence that self-reported exposures to diagnostic ionizing radiation, including computerized tomography (CT) scans, is associated with increased risk of adult glioma. While no independent association was observed for CT scans alone (3+ scans compared to none P = 0.08 and 1-2 scans compared to none P = 0.68), our findings suggest an increased risk of adult gliomas with cumulative exposure to three or more CT scans to the head and neck region (OR = 1.97, 95% CI: 0.92-4.23) limited to those who reported a family history of cancer: the P value for the interaction between having three or more CT scans and family history of cancer was 0.08. The stratum-specific adjusted OR for those with family history of cancer was more than three times that for the sub-group without family history of cancer. While there is some potential for symptom-related bias, one might expect this to be present for all diagnostic procedures rather than specific to one procedure. The interaction between CT scans and glioma with family history of cancer supports the biological plausibility of our findings, because similar results have been found for breast cancer and radiation. This observational data will increase awareness about potential risks associated with CT scans and the need to minimize the use of unnecessary examinations.

Authors
Davis, F; Il'yasova, D; Rankin, K; McCarthy, B; Bigner, DD
MLA Citation
Davis, F, Il'yasova, D, Rankin, K, McCarthy, B, and Bigner, DD. "Medical diagnostic radiation exposures and risk of gliomas." Radiat Res 175.6 (June 2011): 790-796.
PMID
21466382
Source
pubmed
Published In
Radiation Research
Volume
175
Issue
6
Publish Date
2011
Start Page
790
End Page
796
DOI
10.1667/RR2186.1

Effects of aerobic training on oxidative status in postsurgical non-small cell lung cancer patients: a pilot study.

BACKGROUND: Oxidative stress is postulated to contribute to the initiation, promotion, and progression of non-small cell lung cancer (NSCLC). We investigated the effects of supervised, moderate-intensity aerobic training on urinary markers of oxidative status in patients with postsurgical NSCLC. PATIENTS AND METHODS: Sixteen patients with histologically confirmed stage I-IIIB NSCLC were recruited. Exercise training consisted of aerobic cycle ergometry sessions at 60 to ≥70% of baseline peak workload 20-45 min·d(-1), 3 d·wk(-1)for 14 weeks. Oxidative status was assessed via four urinary F(2)-isoprostanes isomers: iPF (2-alpha)-III, 2,3-dinor-iPF(2 alpha)-III, iPF (2-alpha)-VI, and 8,12-iso-iPF(2 alpha)-VI using liquid chromatography with tandem mass spectrometry detection. Peak oxygen consumption (VO2peak) was assessed using a maximal, incremental, cardiopulmonary exercise test with expired gas analysis. RESULTS: A composite index of all four F2-isoprostanes isomers increased from baseline to post-intervention by 32% (p = 0.08). Concerning individual isomers, iPF (2-alpha)-III increased by 0.09 (+55%; p = .010), iPF (2-alpha)-VI by 0.81 (+29%; p = 0.04), and 8,12-iso-iPF(2 alpha)-VI by 0.59 (+28%; p = 0.07) from baseline to postintervention. There was no change in 2,3-dinor-iPF(2 alpha)-III levels. VO2peak increased 1.1 mL·kg·(-1) min(-1) (p = 0.14) and peak workload increased 10 Watts (p < .001). Change in VO2peak was not associated with change in markers of oxidative status. CONCLUSIONS: Aerobic training was associated with significant increases in urinary measures of oxidative status in postsurgical NSCLC. The clinical implications of these findings are currently unknown. Further studies are required to elucidate the complex relationship between aerobic training, oxidative stress, tumor biology, and response to cytotoxic agents in mouse and human models of cancer.

Authors
Jones, LW; Eves, ND; Spasojevic, I; Wang, F; Il'yasova, D
MLA Citation
Jones, LW, Eves, ND, Spasojevic, I, Wang, F, and Il'yasova, D. "Effects of aerobic training on oxidative status in postsurgical non-small cell lung cancer patients: a pilot study." Lung Cancer 72.1 (April 2011): 45-51.
PMID
20863590
Source
pubmed
Published In
Lung Cancer
Volume
72
Issue
1
Publish Date
2011
Start Page
45
End Page
51
DOI
10.1016/j.lungcan.2010.08.002

Risk factors for oligodendroglial tumors: a pooled international study.

Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.

Authors
McCarthy, BJ; Rankin, KM; Aldape, K; Bondy, ML; Brännström, T; Broholm, H; Feychting, M; Il'yasova, D; Inskip, PD; Johansen, C; Melin, BS; Ruder, AM; Butler, MA; Scheurer, ME; Schüz, J; Schwartzbaum, JA; Wrensch, MR; Davis, FG
MLA Citation
McCarthy, BJ, Rankin, KM, Aldape, K, Bondy, ML, Brännström, T, Broholm, H, Feychting, M, Il'yasova, D, Inskip, PD, Johansen, C, Melin, BS, Ruder, AM, Butler, MA, Scheurer, ME, Schüz, J, Schwartzbaum, JA, Wrensch, MR, and Davis, FG. "Risk factors for oligodendroglial tumors: a pooled international study." Neuro Oncol 13.2 (February 2011): 242-250.
PMID
21149253
Source
pubmed
Published In
Neuro-Oncology
Volume
13
Issue
2
Publish Date
2011
Start Page
242
End Page
250
DOI
10.1093/neuonc/noq173

Assessment of type of allergy and antihistamine use in the development of glioma.

BACKGROUND: Allergies have been associated with decreased risk of glioma; but, associations between duration and timing of allergies, and antihistamine use and glioma risk have been less consistent. The objective was to investigate this association by analyzing types, number, years since diagnosis, and age at diagnosis of allergies, and information on antihistamine usage, including type, duration, and frequency of exposure. METHODS: Self-report data on medically diagnosed allergies and antihistamine use were obtained for 419 glioma cases and 612 hospital-based controls from Duke University and NorthShore University HealthSystem. RESULTS: High- and low-grade glioma cases were statistically significantly less likely to report any allergy than controls (OR = 0.66, 95% CI: 0.49-0.87 and OR = 0.44, 95% CI: 0.25-0.76, respectively). The number of types of allergies (seasonal, medication, pet, food, and other) was inversely associated with glioma risk in a dose-response manner (P value for trend < 0.05). Age at diagnosis and years since diagnosis of allergies were not associated with glioma risk. Oral antihistamine use was statistically significantly inversely associated with glioma risk, but when stratified by allergy status, remained significant only for those with high-grade glioma and no medically diagnosed allergy. CONCLUSIONS: All types of allergies appear to be protective with reduced risk for those with more types of allergies. Antihistamine use, other than in relationship with allergy status, may not influence glioma risk. IMPACT: A comprehensive study of allergies and antihistamine use using standardized questions and biological markers will be essential to further delineate the biological mechanism that may be involved in brain tumor development.

Authors
McCarthy, BJ; Rankin, K; Il'yasova, D; Erdal, S; Vick, N; Ali-Osman, F; Bigner, DD; Davis, F
MLA Citation
McCarthy, BJ, Rankin, K, Il'yasova, D, Erdal, S, Vick, N, Ali-Osman, F, Bigner, DD, and Davis, F. "Assessment of type of allergy and antihistamine use in the development of glioma." Cancer Epidemiol Biomarkers Prev 20.2 (February 2011): 370-378.
PMID
21300619
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
20
Issue
2
Publish Date
2011
Start Page
370
End Page
378
DOI
10.1158/1055-9965.EPI-10-0948

Individual responses to chemotherapy-induced oxidative stress.

Differences in redox homeostatic control between cancer patients may underlie predisposition to drug resistance and toxicities. To evaluate interindividual differences in redox response among newly diagnosed breast cancer patients undergoing standard chemotherapy, urine samples were collected before (T0), and at 1 (T1) and 24 h (T24) after chemotherapy administration. Oxidative status was assessed by urinary levels of allantoin and four F2-isoprostanes, quantified by LC-MS/MS. In all subjects, biomarker levels increased at T1 and returned to baseline at T24. Analyzing individual responses, two patterns were revealed: 10 subjects showed uniform increases of biomarker levels at T1 ("increase" pattern) and 8 subjects showed mixed (increase/unchanged/decrease) responses for different biomarkers ("mixed" pattern). The increase-pattern group had lower pre-treatment (T0) levels of the biomarkers and showed a sharp increase at T1 (64-141%) with a subsequent decrease at T24. The mixed-pattern group had higher pre-treatment biomarker levels and showed no change in biomarkers either at T1 or at T24. These findings indicate that there may be at least two distinct redox phenotypes with different homeostatic mechanisms balancing oxidative stress in humans. Recognizing redox phenotypes in human populations may lead to more precise assessment of health risks and benefits associated with individual redox make-up, and may also help to identify cancer patients who are especially susceptible to drug resistance and/or drug toxicity.

Authors
Il'yasova, D; Kennedy, K; Spasojevic, I; Wang, F; Tolun, AA; Base, K; Young, SP; Kelly Marcom, P; Marks, J; Millington, DS; Dewhirst, MW
MLA Citation
Il'yasova, D, Kennedy, K, Spasojevic, I, Wang, F, Tolun, AA, Base, K, Young, SP, Kelly Marcom, P, Marks, J, Millington, DS, and Dewhirst, MW. "Individual responses to chemotherapy-induced oxidative stress." Breast Cancer Res Treat 125.2 (January 2011): 583-589.
PMID
20830514
Source
pubmed
Published In
Breast Cancer Research and Treatment
Volume
125
Issue
2
Publish Date
2011
Start Page
583
End Page
589
DOI
10.1007/s10549-010-1158-7

Association between body mass index and mortality in patients with glioblastoma mutliforme.

PURPOSE: To examine the association between obesity and survival in patients with glioblastoma mutliforme (GBM) METHODS: Using a prospective design, 1,259 patients with previously untreated GBM were recruited between 1991 and 2008. Height and weight were self-reported or abstracted from medical records at study entry and used to calculate body mass index (BMI) [weight (kg)/[height (m)](2). Cox proportional models were used to estimate the risk of death associated with BMI as a continuous variable or categorized using established criteria (normal weight, 18.5-24.9 kg/m(2); overweight, 25.0-29.9 kg/m(2); obese, ≥ 30.0 kg/m(2)). RESULTS: Median follow-up was 40 months, and 1,069 (85%) deaths were observed during this period. For all patients, minimal adjusted analyses indicated no significant association between BMI treated as a continuous variable and survival. Compared with patients with a BMI 18.5-24.9 kg/m(2), the minimally adjusted HR for overall survival was 1.08 (95% CI, 0.94-1.24) for a BMI 25-29.9 kg/m(2) and 1.08 (95% CI, 0.91-28) for a BMI ≥ 30.0 kg/m(2). After additional adjustment for adjuvant therapy, the HR for those with a BMI of 25.0-29.9 kg/m(2) was 1.14 (95% CI, 0.99-1.32) and 1.09 (95% CI, 0.91-1.30) for those with a BMI ≥ 30.0 kg/m(2). No significant interactions were revealed for BMI and any demographic variables. CONCLUSION: BMI was not associated with survival in newly diagnosed and previously untreated patients with GBM. Further research investigating the prognostic significance of alternative, quantitative measures of body habitus, and functional performance are required.

Authors
Jones, LW; Ali-Osman, F; Lipp, E; Marcello, JE; McCarthy, B; McCoy, L; Rice, T; Wrensch, M; Il'yasova, D
MLA Citation
Jones, LW, Ali-Osman, F, Lipp, E, Marcello, JE, McCarthy, B, McCoy, L, Rice, T, Wrensch, M, and Il'yasova, D. "Association between body mass index and mortality in patients with glioblastoma mutliforme." Cancer Causes Control 21.12 (December 2010): 2195-2201.
PMID
20838873
Source
pubmed
Published In
Cancer Causes & Control
Volume
21
Issue
12
Publish Date
2010
Start Page
2195
End Page
2201
DOI
10.1007/s10552-010-9639-x

Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation.

There is increasing recognition of familial propensity to glioma as a distinct clinical entity beyond a few rare syndromes; however its genetic basis is poorly understood. The role of p16(INK4A)/p14(ARF) and p53 mutations in sporadic glioma provides a strong rationale for investigating germline mutations in these genes as a cause of familial glioma. To survey the familial glioma phenotype and examine the contribution of germline mutation in p16(INK4A)/p14(ARF) and p53 to the disease we have analyzed a series of 101 index familial cases collected through the GLIOGENE Consortium (http://braintumor.epigenetic.org/). There was little evidence for within family correlations for tumour histology, suggesting generic susceptibility to glial tumors. We did not detect any functional mutations in p16(INK4A) or p14(ARF). One index case with glioblastoma multiforme (GBM) diagnosed at age 54 and had a family history comprised of a paternal aunt with GBM at age 55, carried the p53 R158H mutation, which is predicted to be functional and has previously been implicated as a cause of Li-Fraumeni syndrome. Our findings provide no evidence that p16(INK4A)/p14(ARF) and p53 mutations contribute significantly to familial glioma.

Authors
Robertson, LB; Armstrong, GN; Olver, BD; Lloyd, AL; Shete, S; Lau, C; Claus, EB; Barnholtz-Sloan, J; Lai, R; Il'yasova, D; Schildkraut, J; Bernstein, JL; Olson, SH; Jenkins, RB; Yang, P; Rynearson, AL; Wrensch, M; McCoy, L; Wienkce, JK; McCarthy, B; Davis, F; Vick, NA; Johansen, C; Bødtcher, H; Sadetzki, S; Bruchim, RB-S; Yechezkel, GH; Andersson, U; Melin, BS; Bondy, ML; Houlston, RS
MLA Citation
Robertson, LB, Armstrong, GN, Olver, BD, Lloyd, AL, Shete, S, Lau, C, Claus, EB, Barnholtz-Sloan, J, Lai, R, Il'yasova, D, Schildkraut, J, Bernstein, JL, Olson, SH, Jenkins, RB, Yang, P, Rynearson, AL, Wrensch, M, McCoy, L, Wienkce, JK, McCarthy, B, Davis, F, Vick, NA, Johansen, C, Bødtcher, H, Sadetzki, S, Bruchim, RB-S, Yechezkel, GH, Andersson, U, Melin, BS, Bondy, ML, and Houlston, RS. "Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation." Fam Cancer 9.3 (September 2010): 413-421.
PMID
20455025
Source
pubmed
Published In
Familial Cancer
Volume
9
Issue
3
Publish Date
2010
Start Page
413
End Page
421
DOI
10.1007/s10689-010-9346-5

Allantoin in human urine quantified by ultra-performance liquid chromatography-tandem mass spectrometry.

Uric acid is a potent antioxidant and scavenger of singlet oxygen and other radicals in humans. Allantoin, the predominant product of free radical-induced oxidation of uric acid, is efficiently excreted in the urine and has potential as a biomarker of oxidative stress. We developed a rapid and specific assay for urinary allantoin using ultra-performance liquid chromatography-tandem mass spectrometry suitable for high-throughput clinical studies. The method required minimal sample preparation and was accurate (mean error=6%), precise (intra- and interday imprecision <8%), and sensitive (limit of detection=0.06pmol). Allantoin levels measured in control samples were comparable to literature values.

Authors
Tolun, AA; Zhang, H; Il'yasova, D; Sztáray, J; Young, SP; Millington, DS
MLA Citation
Tolun, AA, Zhang, H, Il'yasova, D, Sztáray, J, Young, SP, and Millington, DS. "Allantoin in human urine quantified by ultra-performance liquid chromatography-tandem mass spectrometry." Anal Biochem 402.2 (July 15, 2010): 191-193.
PMID
20361921
Source
pubmed
Published In
Analytical Biochemistry
Volume
402
Issue
2
Publish Date
2010
Start Page
191
End Page
193
DOI
10.1016/j.ab.2010.03.033

Urinary biomarkers of oxidative status in a clinical model of oxidative assault.

BACKGROUND: We used doxorubicin-based chemotherapy as a clinical model of oxidative assault in humans. METHODS: The study recruited newly diagnosed breast cancer patients (n = 23). Urine samples were collected immediately before (T0) and at 1 hour (T1) and 24 hours (T24) after i.v. administration of treatment. Measurements included allantoin and the isoprostanes iPF(2alpha)-III, iPF(2alpha)-VI, and 8,12-iso-iPF(2alpha)-VI along with the prostaglandin 2,3-dinor-iPF(2alpha)-III, a metabolite of iPF(2alpha)-III. All biomarkers were quantified using liquid chromatography-tandem mass spectrometry. RESULTS: In all subjects, the levels of the biomarkers increased at T1: allantoin by 22% (P = 0.06), iPF(2alpha)-III by 62% (P < 0.05), iPF(2alpha)-VI by 41% (P < 0.05), 8,12-iso-iPF(2alpha)-VI by 58% (P < 0.05), and 2,3-dinor-iPF(2alpha)-III by 52% (P < 0.05). At T24, the F2-isoprostanes returned to their baseline levels; the levels of allantoin continued to increase, although the T24-T0 difference was not statistically significant. CONCLUSIONS: These results indicate that urinary F2-isoprostanes are valid biomarkers and allantoin is a promising biomarker of oxidative status in humans. IMPACT: The levels of biomarkers change quickly in response to oxidative assault and can be used to monitor oxidative status in humans in response to treatments related either to generation of free radicals (chemotherapy and radiation therapy) or to antioxidants (inborn metabolic diseases and Down syndrome).

Authors
Il'yasova, D; Spasojevic, I; Wang, F; Tolun, AA; Base, K; Young, SP; Marcom, PK; Marks, J; Mixon, G; DiGiulio, R; Millington, DS
MLA Citation
Il'yasova, D, Spasojevic, I, Wang, F, Tolun, AA, Base, K, Young, SP, Marcom, PK, Marks, J, Mixon, G, DiGiulio, R, and Millington, DS. "Urinary biomarkers of oxidative status in a clinical model of oxidative assault." Cancer Epidemiol Biomarkers Prev 19.6 (June 2010): 1506-1510.
PMID
20501773
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
19
Issue
6
Publish Date
2010
Start Page
1506
End Page
1510
DOI
10.1158/1055-9965.EPI-10-0211

Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma.

BACKGROUND: Malignant glioma is a rare cancer with poor survival. The influence of diet and antioxidant intake on glioma survival is not well understood. The current study examines the association between antioxidant intake and survival after glioma diagnosis. METHODS: Adult patients diagnosed with malignant glioma during 1991-1994 and 1997-2001 were enrolled in a population-based study. Diagnosis was confirmed by review of pathology specimens. A modified food-frequency questionnaire interview was completed by each glioma patient or a designated proxy. Intake of each food item was converted to grams consumed/day. From this nutrient database, 16 antioxidants, calcium, a total antioxidant index and 3 macronutrients were available for survival analysis. Cox regression estimated mortality hazard ratios associated with each nutrient and the antioxidant index adjusting for potential confounders. Nutrient values were categorized into tertiles. Models were stratified by histology (Grades II, III, and IV) and conducted for all (including proxy) subjects and for a subset of self-reported subjects. RESULTS: Geometric mean values for 11 fat-soluble and 6 water-soluble individual antioxidants, antioxidant index and 3 macronutrients were virtually the same when comparing all cases (n=748) to self-reported cases only (n=450). For patients diagnosed with Grade II and Grade III histology, moderate (915.8-2118.3 mcg) intake of fat-soluble lycopene was associated with poorer survival when compared to low intake (0.0-914.8 mcg), for self-reported cases only. High intake of vitamin E and moderate/high intake of secoisolariciresinol among Grade III patients indicated greater survival for all cases. In Grade IV patients, moderate/high intake of cryptoxanthin and high intake of secoisolariciresinol were associated with poorer survival among all cases. Among Grade II patients, moderate intake of water-soluble folate was associated with greater survival for all cases; high intake of vitamin C and genistein and the highest level of the antioxidant index were associated with poorer survival for all cases. CONCLUSIONS: The associations observed in our study suggest that the influence of some antioxidants on survival following a diagnosis of malignant glioma are inconsistent and vary by histology group. Further research in a large sample of glioma patients is needed to confirm/refute our results.

Authors
DeLorenze, GN; McCoy, L; Tsai, A-L; Quesenberry, CP; Rice, T; Il'yasova, D; Wrensch, M
MLA Citation
DeLorenze, GN, McCoy, L, Tsai, A-L, Quesenberry, CP, Rice, T, Il'yasova, D, and Wrensch, M. "Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma. (Published online)" BMC Cancer 10 (May 19, 2010): 215-.
Website
http://hdl.handle.net/10161/4355
PMID
20482871
Source
pubmed
Published In
BMC Cancer
Volume
10
Publish Date
2010
Start Page
215
DOI
10.1186/1471-2407-10-215

Prospective association between fasting NEFA and type 2 diabetes: impact of post-load glucose.

AIMS/HYPOTHESIS: Elevated fasting NEFAs are thought to promote type 2 diabetes. Three prospective studies support this concept, showing increased diabetes risk associated with fasting NEFA. However, these prospective associations may be confounded by strong cross-sectional correlations between fasting NEFA and metabolic predictors of diabetes. To examine this assumption, we used cohort data from the Insulin Resistance Atherosclerosis Study (IRAS). METHODS: Within the IRAS cohort (n = 902, 145 incident cases), we examined nine metabolic variables for their confounding effect on the fasting NEFA-diabetes association: 2 h glucose; fasting plasma glucose; body mass index; waist circumference; waist-to-hip ratio; weight; insulin sensitivity (S (I)); fasting insulin; and acute insulin response. We compared odds ratios for fasting NEFA (log( e ) transformed and adjusted for age, sex, ethnicity and clinic) before and after inclusion of each metabolic variable into a logistic regression model. RESULTS: Three variables (2 h glucose, BMI and S (I)) cross-sectionally correlated with fasting NEFA (r > or = 0.1, p < 0.05). Unadjusted for metabolic predictors, fasting NEFA levels were positively associated with diabetes risk: OR 1.37 (95% CI 0.87-2.15) per unit on a log scale. All metabolic variables except AIR showed confounding. Inclusion of 2 h glucose reversed the positive association (OR 0.50 [95% CI 0.30-0.82]), whereas other predictors reduced the association to the null. The final model included the variables correlated with baseline fasting NEFA (2 h glucose, BMI and S (I)) and the demographic variables resulting in OR 0.47 (95% CI 0.27-0.81). CONCLUSIONS/INTERPRETATION: Our results indicate that 2 h glucose strongly confounds the prospective association between fasting NEFA and diabetes; carefully adjusted fasting NEFA levels are inversely associated with diabetes risk.

Authors
Il'yasova, D; Wang, F; D'Agostino, RB; Hanley, A; Wagenknecht, LE
MLA Citation
Il'yasova, D, Wang, F, D'Agostino, RB, Hanley, A, and Wagenknecht, LE. "Prospective association between fasting NEFA and type 2 diabetes: impact of post-load glucose." Diabetologia 53.5 (May 2010): 866-874.
PMID
20143044
Source
pubmed
Published In
Diabetologia
Volume
53
Issue
5
Publish Date
2010
Start Page
866
End Page
874
DOI
10.1007/s00125-010-1657-4

Quantification of the oxidative damage biomarker 2,3-dinor-8-isoprostaglandin-F(2alpha) in human urine using liquid chromatography-tandem mass spectrometry.

F(2)-isoprostanes are useful biomarkers of oxidative status in humans. We developed an ultraperformance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify 2,3-dinor-8-iso prostaglandin F(2alpha), a urinary metabolite of 8-iso-prostaglandin F(2alpha.) Urine was purified by solid-phase extraction and analyzed by UPLC-MS/MS with negative-ion electrospray ionization. The method was robust with a mean inaccuracy of 9%, interday and intraday imprecision of 7.5% or lower, and a lower limit of quantification of 0.5 microg/L, equivalent to 0.04 pmol injected onto the column. An analysis time of 6 min was shorter than previously published methods and amenable to large studies.

Authors
Zhang, H; Il'yasova, D; Sztaray, J; Young, SP; Wang, F; Millington, DS
MLA Citation
Zhang, H, Il'yasova, D, Sztaray, J, Young, SP, Wang, F, and Millington, DS. "Quantification of the oxidative damage biomarker 2,3-dinor-8-isoprostaglandin-F(2alpha) in human urine using liquid chromatography-tandem mass spectrometry." Anal Biochem 399.2 (April 15, 2010): 302-304.
PMID
20026293
Source
pubmed
Published In
Analytical Biochemistry
Volume
399
Issue
2
Publish Date
2010
Start Page
302
End Page
304
DOI
10.1016/j.ab.2009.12.024

Dynamic determinants of longevity and exceptional health.

It is well known from epidemiology that values of indices describing physiological state in a given age may influence human morbidity and mortality risks. Studies of connection between aging and life span suggest a possibility that dynamic properties of age trajectories of the physiological indices could also be important contributors to morbidity and mortality risks. In this paper we use data on longitudinal changes in body mass index, diastolic blood pressure, pulse pressure, pulse rate, blood glucose, hematocrit, and serum cholesterol in the Framingham Heart Study participants, to investigate this possibility in depth. We found that some of the variables describing individual dynamics of the age-associated changes in physiological indices influence human longevity and exceptional health more substantially than the variables describing physiological state. These newly identified variables are promising targets for prevention aiming to postpone onsets of common elderly diseases and increase longevity.

Authors
Yashin, AI; Arbeev, KG; Akushevich, I; Arbeeva, L; Kravchenko, J; Il'yasova, D; Kulminski, A; Akushevich, L; Culminskaya, I; Wu, D; Ukraintseva, SV
MLA Citation
Yashin, AI, Arbeev, KG, Akushevich, I, Arbeeva, L, Kravchenko, J, Il'yasova, D, Kulminski, A, Akushevich, L, Culminskaya, I, Wu, D, and Ukraintseva, SV. "Dynamic determinants of longevity and exceptional health." Current gerontology and geriatrics research (January 2010).
PMID
20953403
Source
epmc
Published In
Current Gerontology and Geriatrics Research
Publish Date
2010
DOI
10.1155/2010/381637

Erratum: Survey of familial glioma and role of germline p16 INK4A/p14ARF and p53 mutation (Familial Cancer DOI: 10.1007/s10689-010-9346-5)

Authors
Robertson, LB; Armstrong, GN; Olver, BD; Lloyd, AL; Shete, S; Lau, C; Claus, EB; Barnholtz-Sloan, J; Lai, R; Il'yasova, D; Schildkraut, J; Bernstein, JL; Olson, SH; Jenkins, RB; Yang, P; Rynearson, AL; Wrensch, M; McCoy, L; Wienkce, JK; McCarthy, B; Davis, F; Vick, NA; Johansen, C; Bødtcher, H; Sadetzki, S; Bruchim, RB-S; Yechezkel, GH; Andersson, U; Melin, BS; Bondy, ML; Houlston, RS
MLA Citation
Robertson, LB, Armstrong, GN, Olver, BD, Lloyd, AL, Shete, S, Lau, C, Claus, EB, Barnholtz-Sloan, J, Lai, R, Il'yasova, D, Schildkraut, J, Bernstein, JL, Olson, SH, Jenkins, RB, Yang, P, Rynearson, AL, Wrensch, M, McCoy, L, Wienkce, JK, McCarthy, B, Davis, F, Vick, NA, Johansen, C, Bødtcher, H, Sadetzki, S, Bruchim, RB-S, Yechezkel, GH, Andersson, U, Melin, BS, Bondy, ML, and Houlston, RS. "Erratum: Survey of familial glioma and role of germline p16 INK4A/p14ARF and p53 mutation (Familial Cancer DOI: 10.1007/s10689-010-9346-5)." Familial Cancer 9.3 (2010): 423-424.
Source
scival
Published In
Familial Cancer
Volume
9
Issue
3
Publish Date
2010
Start Page
423
End Page
424
DOI
10.1007/s10689-010-9353-6

Total dietary antioxidant index and survival in patients with glioblastoma multiforme.

OBJECTIVES: The role of antioxidants in survival of cancer patients is controversial. No data on the relationships between antioxidant intake and survival of glioma patients are available. Our objective was to examine such association in a large series of cases. METHODS: The study population includes 814 glioblastoma multiforme cases that were newly diagnosed, histologically confirmed, aged 20 or older, and residing in the San Francisco Bay Area at diagnosis. Cases were identified via the regional cancer registry's rapid case ascertainment system during 1991-1994 (series I), 1997-2000 (series II), and 2001-2004 (series III). Daily dietary antioxidant intake at diagnosis was assessed via food-frequency questionnaire and was expressed as total antioxidant index, calculated based on Trolox equivalent per gram of food. In addition, the study collected information on supplements/vitamin intake. RESULTS: Overall, our results indicated no consistent, significant association of survival with dietary antioxidant intake or its combination with vitamin supplements. However, in series III, we observed a significant association between higher antioxidant index and better survival: HR = 0.58 (95% CI: 0.46, 0.74) for each unit of antioxidant index on a log-scale. CONCLUSIONS: Although it is possible that this is a chance finding, the association between dietary antioxidants and survival in the most recently recruited patients warrants further investigations.

Authors
Il'yasova, D; Marcello, JE; McCoy, L; Rice, T; Wrensch, M
MLA Citation
Il'yasova, D, Marcello, JE, McCoy, L, Rice, T, and Wrensch, M. "Total dietary antioxidant index and survival in patients with glioblastoma multiforme." Cancer Causes Control 20.8 (October 2009): 1255-1260.
PMID
19363672
Source
pubmed
Published In
Cancer Causes & Control
Volume
20
Issue
8
Publish Date
2009
Start Page
1255
End Page
1260
DOI
10.1007/s10552-009-9338-7

Markers of oxidative status in a clinical model of oxidative assault: a pilot study in human blood following doxorubicin administration.

We used doxorubicin-based chemotherapy as a clinical model for oxidative assault. Study recruited 23 breast cancer patients and collected blood samples before (T0), at 1 (T1) and 24 hours (T24) after treatment administration. Measurements included protein carbonyl content (PPCC), malondialdehyde (MDA), and alpha- and gamma-tocopherols in plasma and total glutathione content in erythrocytes (erGSHt). In all subjects, PPCC and MDA levels did not change. erGSHt levels increased at T24 by 8% (p=0.03). Levels of alpha, gamma, and total tocopherols progressively decreased by 7%-15% (p <0.05). In subjects with low erGSHt levels (below median), PPCC mean levels progressively increased from 0.35 (T0) to 0.56 (T1) and 0.72 nmol carbonyl/mg protein (T24) (p =0.2). These results indicate that (1) plasma MDA is not a sensitive biomarker in humans; (2) PPCC potentially may be used, if antioxidant reserves are taken into account; (3) antioxidant reserves play an important role in the reaction to oxidative stress.

Authors
Il'yasova, D; Mixon, G; Wang, F; Marcom, PK; Marks, J; Spasojevich, I; Craft, N; Arredondo, F; DiGiulio, R
MLA Citation
Il'yasova, D, Mixon, G, Wang, F, Marcom, PK, Marks, J, Spasojevich, I, Craft, N, Arredondo, F, and DiGiulio, R. "Markers of oxidative status in a clinical model of oxidative assault: a pilot study in human blood following doxorubicin administration." Biomarkers 14.5 (August 2009): 321-325.
PMID
19476408
Source
pubmed
Published In
Biomarkers (Informa)
Volume
14
Issue
5
Publish Date
2009
Start Page
321
End Page
325
DOI
10.1080/13547500902946757

Association between glioma and history of allergies, asthma, and eczema: a case-control study with three groups of controls.

Because glioma etiology is largely unknown, the inverse association of glioma risk with atopic conditions is promising and deserves close scrutiny. We examined the association between a history of allergies, asthma, and eczema, and glioma risk using sibling, friend, and clinic-based controls. This analysis included 388 incident glioma cases and 80 sibling, 191 friend, and 177 clinic-based controls. Each subject's medical history was assessed via a Web-based or telephone survey. Odds ratios (OR) and their 95% confidence intervals (CI) for the associations with allergies, asthma, eczema, and the overall number of these conditions were calculated from conditional (for sibling and friend controls) and unconditional (for clinic-based controls) logistic models. Allergies were consistently inversely associated with the glioma: ORs were 0.53 (95% CI, 0.15-1.84), 0.54 (95% CI, 0.28-1.07), and 0.34 (95% CI, 0.23-0.50) with sibling, friend, and clinic-based controls, respectively. Asthma showed an inverse association only in the comparison with sibling controls (OR, 0.43; 95% CI, 0.19-1.00). Eczema showed an inverse association only in the comparison with friend controls (OR, 0.42; 95% CI, 0.15-1.18). The overall number of these conditions (ordinal score 0, 1, 2, 3) was inversely associated with glioma: The risk decreased 31% to 45% with each addition of an atopic condition. These estimates were the most stable when different control groups were considered. Comparing the prevalence of these conditions in the three control groups with published data, we note that clinic-based controls generally better approximate the prevalence data for population-based groups. These controls seem to present a reasonable choice for clinic-centered case-control studies.

Authors
Il'yasova, D; McCarthy, B; Marcello, J; Schildkraut, JM; Moorman, PG; Krishnamachari, B; Ali-Osman, F; Bigner, DD; Davis, F
MLA Citation
Il'yasova, D, McCarthy, B, Marcello, J, Schildkraut, JM, Moorman, PG, Krishnamachari, B, Ali-Osman, F, Bigner, DD, and Davis, F. "Association between glioma and history of allergies, asthma, and eczema: a case-control study with three groups of controls." Cancer Epidemiol Biomarkers Prev 18.4 (April 2009): 1232-1238.
PMID
19336556
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
18
Issue
4
Publish Date
2009
Start Page
1232
End Page
1238
DOI
10.1158/1055-9965.EPI-08-0995

Human exposure to selected animal neurocarcinogens: a biomarker-based assessment and implications for brain tumor epidemiology.

This review is based on the proceedings from the Second Lebow Conference, held in Chicago in 2007. The conference concentrated on developing a framework for innovative studies in the epidemiology of environmental exposures, focusing specifically on the potential relationship with brain tumors. Researchers with different perspectives, including toxicology, pharmacokinetics, and epidemiological exposure assessment, exchanged information and ideas on the use of biomarkers of exposure in molecular epidemiology studies and summarized the current knowledge on methods and approaches for biomarker-based exposure assessment. This report presents the state of science regarding biomarker-based exposure assessment of the four most common neurocarcinogens: acrylamide, 1,3-butadiene, N-nitroso compounds, and polycyclic aromatic hydrocarbons. Importantly, these chemicals are also carcinogenic in other organs; therefore, this discussion is useful for environmental epidemiologists studying all cancer types.

Authors
Il'yasova, D; McCarthy, BJ; Erdal, S; Shimek, J; Goldstein, J; Doerge, DR; Myers, SR; Vineis, P; Wishnok, JS; Swenberg, JA; Bigner, DD; Davis, FG
MLA Citation
Il'yasova, D, McCarthy, BJ, Erdal, S, Shimek, J, Goldstein, J, Doerge, DR, Myers, SR, Vineis, P, Wishnok, JS, Swenberg, JA, Bigner, DD, and Davis, FG. "Human exposure to selected animal neurocarcinogens: a biomarker-based assessment and implications for brain tumor epidemiology." J Toxicol Environ Health B Crit Rev 12.3 (March 2009): 175-187. (Review)
PMID
19466671
Source
pubmed
Published In
Journal of Toxicology and Environmental Health Part B: Critical Reviews
Volume
12
Issue
3
Publish Date
2009
Start Page
175
End Page
187
DOI
10.1080/10937400902894152

Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium.

Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the group's consensus on the current state of scientific findings, and they present a consensus on research priorities to identify which important areas the science should move to address.

Authors
Bondy, ML; Scheurer, ME; Malmer, B; Barnholtz-Sloan, JS; Davis, FG; Il'yasova, D; Kruchko, C; McCarthy, BJ; Rajaraman, P; Schwartzbaum, JA; Sadetzki, S; Schlehofer, B; Tihan, T; Wiemels, JL; Wrensch, M; Buffler, PA; Brain Tumor Epidemiology Consortium,
MLA Citation
Bondy, ML, Scheurer, ME, Malmer, B, Barnholtz-Sloan, JS, Davis, FG, Il'yasova, D, Kruchko, C, McCarthy, BJ, Rajaraman, P, Schwartzbaum, JA, Sadetzki, S, Schlehofer, B, Tihan, T, Wiemels, JL, Wrensch, M, Buffler, PA, and Brain Tumor Epidemiology Consortium, . "Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium." Cancer 113.7 Suppl (October 1, 2008): 1953-1968. (Review)
PMID
18798534
Source
pubmed
Published In
Cancer
Volume
113
Issue
7 Suppl
Publish Date
2008
Start Page
1953
End Page
1968
DOI
10.1002/cncr.23741

Comparing the reliability of responses to telephone-administered versus self-administered Web-based surveys in a case-control study of adult malignant brain cancer.

INTRODUCTION: To determine whether a Web-based survey was an acceptable method of data collection for a clinic-based case-control study of adult brain cancer, the authors compared the reliability of paired responses to a main and resurvey for participants completing surveys by telephone (n=74) or self-administered on the Web (n=465) between 2003 and 2006. METHODS: Recruitment of cases was done at the Evanston Northwestern Healthcare Kellogg Cancer Care Center and the Duke University Medical Center Cancer Control division, and controls were friends and siblings of cases. Twenty-five variables were examined, including smoking, oral contraceptive and residential histories, water sources, meat preparation, fruit and vegetable consumption, and pesticide use. Weighted and simple kappa's were estimated for categorical and binary variables, respectively. RESULTS: The number of concordant paired responses was summed for use in linear regression. Respondents were 97% White and 85% had postsecondary education. Kappa's for individual questions ranged from 0.31 (duration of residence in a single family house) to 0.96 (ever smoked), with a median of 0.57 (95% confidence interval, 0.47-0.64). The median number of concordant responses was 16.2 (range, 5-22). Reliability was greater for controls than cases, Web-based versus telephone responders, females, and higher-income responders. Frequency of e-mail and Internet use was not associated with reliability. CONCLUSIONS: A self-administered, Web-based survey was a feasible and appropriate mode of interview in this study. The comparable reliability of Web compared with telephone responses suggest that Web-based self-interviews could be a cost-effective alternative to traditional modes of interview.

Authors
Rankin, KM; Rauscher, GH; McCarthy, B; Erdal, S; Lada, P; Il'yasova, D; Davis, F
MLA Citation
Rankin, KM, Rauscher, GH, McCarthy, B, Erdal, S, Lada, P, Il'yasova, D, and Davis, F. "Comparing the reliability of responses to telephone-administered versus self-administered Web-based surveys in a case-control study of adult malignant brain cancer." Cancer Epidemiol Biomarkers Prev 17.10 (October 2008): 2639-2646.
PMID
18843005
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
17
Issue
10
Publish Date
2008
Start Page
2639
End Page
2646
DOI
10.1158/1055-9965.EPI-08-0304

The association between serum copper and anaemia in the adult Second National Health and Nutrition Examination Survey (NHANES II) population.

Though common in older adults, anaemia is unexplained in about one-third of cases. As a rare cause of anaemia and neutropenia, Cu deficiency could account for some cases of unexplained anaemia. We examined the relationship between serum Cu and unexplained anaemia among 11,240 participants in the Second National Health and Nutrition Examination Survey (NHANES II): 638 (5.7% of all adults) were anaemic; 421 (3.7%) were not explained by deficiencies of vitamin B12, folate or Fe, chronic illness or renal disease. Spline regression showed a U-shaped relationship between serum Cu levels and unexplained anaemia, indicating that both high and low serum Cu levels are associated with unexplained anaemia in adults. Chronic inflammation and mild Fe deficiency could account for the association between unexplained anaemia and elevated Cu levels. On the other hand, the finding of hypocupraemia in a subset of adults with unexplained anaemia suggests that Cu deficiency may be a common reversible cause of anaemia in adults.

Authors
Knovich, MA; Il'yasova, D; Ivanova, A; Molnár, I
MLA Citation
Knovich, MA, Il'yasova, D, Ivanova, A, and Molnár, I. "The association between serum copper and anaemia in the adult Second National Health and Nutrition Examination Survey (NHANES II) population." Br J Nutr 99.6 (June 2008): 1226-1229.
PMID
18533287
Source
pubmed
Published In
The British journal of nutrition
Volume
99
Issue
6
Publish Date
2008
Start Page
1226
End Page
1229

Health-protective and adverse effects of the apolipoprotein E epsilon2 allele in older men.

OBJECTIVES: To reexamine a health-protective role of the common apolipoprotein E (APOE) polymorphism focusing on connections between the APOE epsilon2-containing genotypes and impairments in instrumental activities of daily living (IADLs) in older (> or = 65) men and women and to examine how diagnosed coronary heart disease (CHD), Alzheimer's disease, colorectal cancer, macular degeneration, and atherosclerosis may mediate these connections. DESIGN: Retrospective cross-sectional study. SETTING: The unique disability-focused data from a genetic subsample of the 1999 National Long Term Care Survey linked with Medicare service use files. PARTICIPANTS: One thousand seven hundred thirty-three genotyped individuals interviewed regarding IADL disabilities. MEASUREMENTS: Indicators of IADL impairments, five geriatric disorders, and epsilon2-containing genotypes. RESULTS: The epsilon2/3 genotype is a major contributor to adverse associations between the epsilon2 allele and IADL disability in men (odds ratio (OR)=3.09, 95% confidence interval (CI)=1.53-6.26), although it provides significant protective effects for CHD (OR=0.55, 95% CI=0.33-0.92), whereas CHD is adversely associated with IADL disability (OR=2.18, 95% CI=1.28-3.72). Adjustment for five diseases does not significantly alter the adverse association between epsilon2-containing genotypes and disability. Protective effects of the epsilon2/3 genotype for CHD (OR=0.52, 95% CI=0.27-0.99) and deleterious effects for IADLs (OR=3.50, 95% CI=1.71-7.14) for men hold in multivariate models with both these factors included. No significant associations between the epsilon2-containing genotypes and IADL are found in women. CONCLUSION: The epsilon2 allele can play a dual role in men, protecting them against some health disorders, while promoting others. Strong adverse relationships with disability suggest that epsilon2-containing genotypes can be unfavorable factors for the health and well-being of aging men.

Authors
Kulminski, AM; Ukraintseva, SV; Arbeev, KG; Manton, KG; Oshima, J; Martin, GM; Il'yasova, D; Yashin, AI
MLA Citation
Kulminski, AM, Ukraintseva, SV, Arbeev, KG, Manton, KG, Oshima, J, Martin, GM, Il'yasova, D, and Yashin, AI. "Health-protective and adverse effects of the apolipoprotein E epsilon2 allele in older men." J Am Geriatr Soc 56.3 (March 2008): 478-483.
PMID
18179501
Source
pubmed
Published In
Journal of American Geriatrics Society
Volume
56
Issue
3
Publish Date
2008
Start Page
478
End Page
483
DOI
10.1111/j.1532-5415.2007.01574.x

Correlation between two markers of inflammation, serum C-reactive protein and interleukin 6, and indices of oxidative stress in patients with high risk of cardiovascular disease.

As evidence of the involvement of inflammation and oxidative damage in pathogenesis of age-related chronic diseases is growing, epidemiologists need to develop measures of both conditions to study their relationships in human populations. One way of searching for appropriate biomarkers is to examine correlations between different inflammatory markers and oxidative indices. We examined cross-sectional correlations between two inflammatory markers, serum C-reactive protein (CRP) and interleukin (IL)-6, and three oxidative indices, plasma levels of alpha-tocopherol and beta-carotene, and urinary levels of 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoP), in 60 individuals at high risk of cardiovascular disease. Correlations between the biomarkers were examined graphically and using the Pearson correlation coefficient. No correlation was found between plasma levels of alpha-tocopherol and either of the inflammatory markers. Plasma beta-carotene inversely correlated with IL-6 (r = -0.46, p=0.0002) and CRP (r = -0.41, p = 0.001). Although urinary F2-IsoP did not correlate with IL-6, this biomarker positively correlated with CRP (r = 0.31, p = 0.002). As only urinary F2-IsoP levels have been validated against known oxidative assaults, their positive association with CRP levels is interpreted as evidence of an interconnection between low-level inflammation and oxidative status. Urinary levels of F2-IsoP and serum levels of CRP represent appropriate biomarkers for future studies of inflammation and oxidative status in humans.

Authors
Il'yasova, D; Ivanova, A; Morrow, JD; Cesari, M; Pahor, M
MLA Citation
Il'yasova, D, Ivanova, A, Morrow, JD, Cesari, M, and Pahor, M. "Correlation between two markers of inflammation, serum C-reactive protein and interleukin 6, and indices of oxidative stress in patients with high risk of cardiovascular disease." Biomarkers 13.1 (February 2008): 41-51.
PMID
17852073
Source
pubmed
Published In
Biomarkers (Informa)
Volume
13
Issue
1
Publish Date
2008
Start Page
41
End Page
51
DOI
10.1080/13547500701617708

GLIOGENE an International Consortium to Understand Familial Glioma.

Evidence for familial aggregation of glioma has been documented in both case-control and cohort studies and occurs apart from the well-described rare inherited genetic syndromes involving glioma: neurofibromatosis type 1 and 2, tuberous sclerosis, Turcot's syndrome, and Li-Fraumeni syndrome. Nonsyndromic glioma families have been studied but no genes have been identified in the two published linkage studies of familial glioma probably due to the small number of families. Because glioma is a rare but devastating cancer, and a family history of glioma has been observed in approximately 5% of the cases, we initiated an international consortium to identify glioma families not affected by syndromes to better understand the inherited factors related to this disease. The international consortium GLIOGENE is an acronym for "glioma gene" and includes 15 research groups in North America, Europe, and Israel to study familial glioma. The overarching goal is to characterize genes in glioma families using a genome-wide single-nucleotide polymorphism approach and conducting linkage analysis to identify new genomic regions or loci that could harbor genes important for gliomagenesis. Here, we review the rationale for studying familial glioma and our proposed strategy for the GLIOGENE study.

Authors
Malmer, B; Adatto, P; Armstrong, G; Barnholtz-Sloan, J; Bernstein, JL; Claus, E; Davis, F; Houlston, R; Il'yasova, D; Jenkins, R; Johansen, C; Lai, R; Lau, C; McCarthy, B; Nielsen, H; Olson, SH; Sadetzki, S; Shete, S; Wiklund, F; Wrensch, M; Yang, P; Bondy, M
MLA Citation
Malmer, B, Adatto, P, Armstrong, G, Barnholtz-Sloan, J, Bernstein, JL, Claus, E, Davis, F, Houlston, R, Il'yasova, D, Jenkins, R, Johansen, C, Lai, R, Lau, C, McCarthy, B, Nielsen, H, Olson, SH, Sadetzki, S, Shete, S, Wiklund, F, Wrensch, M, Yang, P, and Bondy, M. "GLIOGENE an International Consortium to Understand Familial Glioma." Cancer Epidemiol Biomarkers Prev 16.9 (September 2007): 1730-1734. (Review)
PMID
17855690
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
16
Issue
9
Publish Date
2007
Start Page
1730
End Page
1734
DOI
10.1158/1055-9965.EPI-07-0081

Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort.

BACKGROUND: Chronic inflammation is associated with processes that contribute to the onset or progression of cancer. This study examined the relationships between circulating levels of the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) and total as well as site-specific cancer incidence. METHODS: Study subjects (n = 2,438) were older adults (ages 70-79 years) participating in the Health Aging and Body Composition study, who did not report a previous cancer diagnosis (except for nonmelanoma skin cancer) at baseline. Incident cancer events (n = 296) were ascertained during an average follow-up of 5.5 years. Inflammatory markers were measured in stored baseline fasting blood samples. RESULTS: The adjusted hazard ratios (95% confidence intervals) for incident cancer associated with a 1-unit increase on the natural log-scale were 1.13 (0.94-1.37), 1.25 (1.09-1.43), and 1.28 (0.96-1.70) for IL-6, CRP, and TNF-alpha, respectively. Markers were more strongly associated with cancer death: hazard ratios were 1.63 (1.19-2.23) for IL-6, 1.64 (1.20-2.24) for CRP, and 1.82 (1.14-2.92) for TNF-alpha. Although precision was low for site-specific analyses, our results suggest that all three markers were associated with lung cancer, that IL-6 and CRP were associated with colorectal cancer, and that CRP was associated with breast cancer. Prostate cancer was not associated with any of these markers. CONCLUSIONS: These findings suggest that (a) the associations between IL-6, CRP, and TNF-alpha and the risk of cancer may be site specific and (b) increased levels of inflammatory markers are more strongly associated with the risk of cancer death than cancer incidence.

Authors
Il'yasova, D; Colbert, LH; Harris, TB; Newman, AB; Bauer, DC; Satterfield, S; Kritchevsky, SB
MLA Citation
Il'yasova, D, Colbert, LH, Harris, TB, Newman, AB, Bauer, DC, Satterfield, S, and Kritchevsky, SB. "Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort." Cancer Epidemiol Biomarkers Prev 14.10 (October 2005): 2413-2418.
PMID
16214925
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
14
Issue
10
Publish Date
2005
Start Page
2413
End Page
2418
DOI
10.1158/1055-9965.EPI-05-0316

Cadmium and renal cancer.

BACKGROUND: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. METHODS: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. RESULTS: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. CONCLUSIONS: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine.

Authors
Il'yasova, D; Schwartz, GG
MLA Citation
Il'yasova, D, and Schwartz, GG. "Cadmium and renal cancer." Toxicol Appl Pharmacol 207.2 (September 1, 2005): 179-186. (Review)
PMID
16102569
Source
pubmed
Published In
Toxicology and Applied Pharmacology
Volume
207
Issue
2
Publish Date
2005
Start Page
179
End Page
186
DOI
10.1016/j.taap.2004.12.005

Urinary F2-isoprostanes are not associated with increased risk of type 2 diabetes.

OBJECTIVE: Free radicals have been implicated in the etiology of type 2 diabetes. Cross-sectional studies have demonstrated associations between oxidative damage and type 2 diabetes. However, no prospective data on this association are available. RESEARCH METHODS AND PROCEDURES: A case control study was conducted within the prospective cohort of the Insulin Resistance Atherosclerosis Study: 26 cases who developed type 2 diabetes in the follow-up period and 26 controls who remained free of type 2 diabetes were randomly selected. Oxidative status was assessed by measuring 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoPM) in baseline urine samples using gas chromatography/mass spectroscopy. Type 2 diabetes was defined by serial oral glucose tolerance tests and World Health Organization criteria. RESULTS: Urinary F2-IsoPM varied between 0.18 and 2.60 ng/mg creatinine; 25th/50th/75th percentiles were 0.42, 0.60, and 0.89, respectively. A trend toward higher levels were observed in women and in persons with impaired glucose tolerance at baseline (p = 0.1). F2-IsoPM increased with BMI (r = 0.36, p = 0.01). After adjustment for age, gender, baseline impaired glucose tolerance status, and BMI, F2-IsoPM levels were inversely associated with development of type 2 diabetes: odds ratio = 0.32 (95% confidence interval, 0.12 to 0.81) for the difference between the 75th and 25th percentiles. DISCUSSION: These results suggest that oxidative damage is not a cause of type 2 diabetes. Positive cross-sectional associations of F2-IsoPM with the risk factors for diabetes, BMI, and impaired glucose tolerance and inverse associations with development of type 2 diabetes indicate that F2-IsoPM might reflect a compensatory mechanism.

Authors
Il'yasova, D; Morrow, JD; Wagenknecht, LE
MLA Citation
Il'yasova, D, Morrow, JD, and Wagenknecht, LE. "Urinary F2-isoprostanes are not associated with increased risk of type 2 diabetes." Obes Res 13.9 (September 2005): 1638-1644.
PMID
16222068
Source
pubmed
Published In
Obesity research
Volume
13
Issue
9
Publish Date
2005
Start Page
1638
End Page
1644
DOI
10.1038/oby.2005.201

Choice of exposure scores for categorical regression in meta-analysis: a case study of a common problem.

OBJECTIVE: Reporting categorical relative risk estimates for a series of exposure levels versus a common reference category is a widespread practice. In meta-analysis, categorical regression estimates a dose-response trend from such results. This method requires the assignment of a single score to each exposure category. We examined how closely meta-analytical categorical regression approximates the results of analysis based on the individual-level continuous exposure. METHODS: The analysis included five studies on tea intake and outcomes related to colorectal cancer. In addition, we derived categorical mean and median values from published distributions of tea consumption in similar populations to assign scores to the categories of tea intake when possible. We examined whether these derived mean and median values well approximate the individual-level results. RESULTS: In meta-analytical categorical regression, using the midrange scores approximated the individual-level continuous analyses reasonably well, if the value assigned to the uppermost, open-ended category was at least as high as the lower bound plus the width of the second-highest category. Categorical mean values derived from the published distributions of regular tea (in the US) and green tea (in Japan) well approximated the slope obtained from individual-level analysis. CONCLUSION: Publication of both the categorical and the continuous estimates of effect in primary studies, with their standard errors, can enhance the quality of meta-analysis, as well as providing intrinsically valuable information on dose-response.

Authors
Il'yasova, D; Hertz-Picciotto, I; Peters, U; Berlin, JA; Poole, C
MLA Citation
Il'yasova, D, Hertz-Picciotto, I, Peters, U, Berlin, JA, and Poole, C. "Choice of exposure scores for categorical regression in meta-analysis: a case study of a common problem." Cancer Causes Control 16.4 (May 2005): 383-388. (Review)
PMID
15953980
Source
pubmed
Published In
Cancer Causes & Control
Volume
16
Issue
4
Publish Date
2005
Start Page
383
End Page
388
DOI
10.1007/s10552-004-5025-x

Black tea and cardiovascular disease (multiple letters) [3]

Authors
Tokudome, S; Nahomi, I; Goto, C; Tokudome, Y; Moore, MA; Poole, C; Peters, U; Il'Yasova, D; Arab, L
MLA Citation
Tokudome, S, Nahomi, I, Goto, C, Tokudome, Y, Moore, MA, Poole, C, Peters, U, Il'Yasova, D, and Arab, L. "Black tea and cardiovascular disease (multiple letters) [3]." International Journal of Epidemiology 34.2 (2005): 482-483.
PMID
15743875
Source
scival
Published In
International Journal of Epidemiology
Volume
34
Issue
2
Publish Date
2005
Start Page
482
End Page
483
DOI
10.1093/ije/dyh211

Epidemiological marker for oxidant status: comparison of the ELISA and the gas chromatography/mass spectrometry assay for urine 2,3-dinor-5,6-dihydro-15-F2t-isoprostane.

PURPOSE: A biomarker of oxidant status applicable to epidemiological research is essential to studying the relationship between free radicals and chronic disease risk. Gas chromatography with mass-spectrometry detection (GC/MS) is the gold standard for measurement of urinary F2-isoprostanes (F2-isoPs), a non-invasive marker of oxidant status. However, this method is laborious and costly, which prohibits its use in large epidemiological studies. METHODS: We compared GC/MS assay with an inexpensive quick enzyme-linked immunoassay (ELISA) in measurements of 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-isoPM), an abundant beta-oxidation metabolite of 8-iso-prostaglandin-F2alpha. We measured F2-isoPM in urine of 52 participants of the Insulin Resistance Atherosclerosis Study by both methods. RESULTS: The ELISA measurements showed approximately 30-fold greater mean and median (22.10, SD 12.92, and 18.49 ng/mg creatinine) than the GC/MS measurements (0.703, SD 0.468, and 0.597 ng/mg creatinine). We found low linear correlation (Pearson correlation coefficient 0.51; 95% CI, 0.28-0.70) and weak agreement in ranking subjects by tertiles (weighted Kappa statistic 0.34) between a GC/MS and ELISA. CONCLUSIONS: We conclude that the current ELISA method is not a valid substitute for the GS/MS assay.

Authors
Il'yasova, D; Morrow, JD; Ivanova, A; Wagenknecht, LE
MLA Citation
Il'yasova, D, Morrow, JD, Ivanova, A, and Wagenknecht, LE. "Epidemiological marker for oxidant status: comparison of the ELISA and the gas chromatography/mass spectrometry assay for urine 2,3-dinor-5,6-dihydro-15-F2t-isoprostane." Ann Epidemiol 14.10 (November 2004): 793-797.
PMID
15519902
Source
pubmed
Published In
Annals of Epidemiology
Volume
14
Issue
10
Publish Date
2004
Start Page
793
End Page
797
DOI
10.1016/j.annepidem.2004.03.003

The epidemiology of tea consumption and colorectal cancer incidence.

This manuscript provides a brief synopsis of 30 studies aimed at examining tea consumption as a factor in the incidence of colon and rectal cancers. The 30 papers examine populations in 12 countries and provide data on consumption of both black and green tea. These studies do not provide consistent evidence to support the theory from animal studies and basic research that tea is a potent chemopreventive agent. Details of the studies are presented, and the potential impact of measurement error, publication bias, the form of tea consumed, the appropriateness of the outcomes studied and the adjustment of confounders related to both tea consumption and risk of colorectal cancer or polyps in various countries are explored. In general, the data are not more consistent for green than for black tea. Particularly with green tea, the doses consumed do get into a perceived protective range in a significant subset of the population. A negative association is stronger in observational epidemiologic studies of rectal cancer than in colon cancer. There is no consistent adjustment for important potential confounders of any tea relationship, such as coffee and alcohol consumption and physical activity levels. Finally, the assessment of tea in most of these studies was based on a single question and therefore may have significant measurement error compared with more recent studies specifically aimed at assessing tea consumption.

Authors
Arab, L; Il'yasova, D
MLA Citation
Arab, L, and Il'yasova, D. "The epidemiology of tea consumption and colorectal cancer incidence." J Nutr 133.10 (October 2003): 3310S-3318S. (Review)
PMID
14519831
Source
pubmed
Published In
The Journal of nutrition
Volume
133
Issue
10
Publish Date
2003
Start Page
3310S
End Page
3318S

Tea intake and risk of colon cancer in African-Americans and whites: North Carolina colon cancer study.

OBJECTIVES: Tea polyphenols have been shown to exhibit anti-cancer activity, but the epidemiological findings are inconsistent. We examined the association between tea consumption and colon cancer in a population-based study in North Carolina. METHODS: The analysis included 630 cases and 1040 controls frequency matched to cases by age, gender, and race. The odds ratios (OR) for tea consumption, adjusted for age and gender, were calculated for African-Americans and Whites and effect modification by race was explored. RESULTS: No association was found between tea consumption and colon cancer overall. Compared to non-consumers, those who consumed <2 servings/day or > or = 2 servings/day had OR = 0.9 (95% CI: 0.7-1.2) and OR = 1.3 (95% CI: 0.9-1.8) respectively. Other risk factors for colorectal cancer (family history of colorectal cancer, exposure to non-steroid anti-inflammatory drugs, meat cooking practices, smoking, physical activity, body mass index, intake of red meat, fruits, vegetables, and alcoholic beverages) did not influence these associations. We did not find any evidence of effect modification by race on either on the multiplicative or additive scale. CONCLUSION: We conclude that, contrary to expectation, tea drinking did not decrease the risk of colon cancer in this study population.

Authors
Il'yasova, D; Martin, C; Sandler, RS
MLA Citation
Il'yasova, D, Martin, C, and Sandler, RS. "Tea intake and risk of colon cancer in African-Americans and whites: North Carolina colon cancer study." Cancer Causes Control 14.8 (October 2003): 767-772.
PMID
14674741
Source
pubmed
Published In
Cancer Causes & Control
Volume
14
Issue
8
Publish Date
2003
Start Page
767
End Page
772

Tea consumption, apoptosis, and colorectal adenomas.

Induction of apoptosis has been suggested as a mechanism for the anti-carcinogenic effect of tea constituents in animals and in vitro studies. We addressed this hypothesis in a human study. Study participants were consecutive patients who underwent colonoscopy at the UNC Hospitals (August 1998 to March 2000). Biopsies were taken from normal rectal mucosa. Apoptosis was scored by the terminal deoxyribonucleotide transferase-mediated digoxigenin dUTP nick end labeling (TUNEL) method and by standard morphological criteria. The analysis included 171 patients with adenomas (cases) and 323 adenoma-free controls. After adjusting for sex, age, race, and BMI, apoptotic score was inversely associated with adenoma: the odds ratios (ORs) for linear trend associated with tertiles were 0.3 (0.3-0.5) for morphologic score and 0.5 (0.4-0.6) for the TUNEL score, respectively. Tea consumption (2-3 and >3 versus <2 servings/day) showed a weak negative association with adenoma: the ORs were 0.7 (0.3-1.4) and 0.5 (0.2-1.1), respectively. Neither measurement of apoptotic score changed by the level of tea consumption (P value for Kruskal-Wallis test > or =0.5). We did not find statistical interaction between apoptotic score and tea consumption. Tea exposure is not associated with apoptosis in normal rectal tissue in vivo.

Authors
Il'yasova, D; Hodgson, ME; Martin, C; Galanko, J; Sandler, RS
MLA Citation
Il'yasova, D, Hodgson, ME, Martin, C, Galanko, J, and Sandler, RS. "Tea consumption, apoptosis, and colorectal adenomas." Eur J Cancer Prev 12.5 (October 2003): 439-443.
PMID
14512812
Source
pubmed
Published In
European Journal of Cancer Prevention
Volume
12
Issue
5
Publish Date
2003
Start Page
439
End Page
443
DOI
10.1097/01.cej.0000091884.10855.58

Commentary: This study failed?

Authors
Poole, C; Peters, U; Il'yasova, D; Arab, L
MLA Citation
Poole, C, Peters, U, Il'yasova, D, and Arab, L. "Commentary: This study failed?." Int J Epidemiol 32.4 (August 2003): 534-535.
PMID
12913024
Source
pubmed
Published In
International Journal of Epidemiology
Volume
32
Issue
4
Publish Date
2003
Start Page
534
End Page
535

Black tea consumption and risk of rectal cancer in Moscow population.

PURPOSE: This population-based case-control study (663 cases and 323 controls) examined the effect of black tea intake on the risk of rectal cancer in Moscow residents. The Moscow population was selected for its wide range of black tea consumption. METHODS: This study used three measures of tea consumption: the volume of beverage (l/month), zavarka (tea concentrate, l/month), and dry tea (g/month). We calculated the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for these three parameters of tea intake using logistic regression. RESULTS: Greater use of dry tea was associated with lower risk of rectal cancer in women (high vs. low: OR = 0.40; 95% CI, 0.23-0.70) and in men (high vs. low: OR = 0.77; 95% CI, 0.42-1.43). The observed effect was weaker when tea was measured as zavarka (high vs. low in women: OR = 0.47; 95% CI, 0.26-0.83; in men: OR = 0.99; 95% CI, 0.52-1.96) and as beverage volume (high vs. low in women: OR = 0.68; 95% CI, 0.39-1.19; in men: OR = 1.03; 95% CI, 0.53-2.09). CONCLUSIONS: These findings support the hypothesis that black tea consumption reduces the risk of rectal cancer. The attenuation of the effect across the three measures of tea intake can be explained by an increasing degree of exposure misclassification from dry tea to zavarka and beverage volume.

Authors
Dora, I; Arab, L; Martinchik, A; Sdvizhkov, A; Urbanovich, L; Weisgerber, U
MLA Citation
Dora, I, Arab, L, Martinchik, A, Sdvizhkov, A, Urbanovich, L, and Weisgerber, U. "Black tea consumption and risk of rectal cancer in Moscow population." Ann Epidemiol 13.6 (July 2003): 405-411.
PMID
12875797
Source
pubmed
Published In
Annals of Epidemiology
Volume
13
Issue
6
Publish Date
2003
Start Page
405
End Page
411

Urinary cadmium, impaired fasting glucose, and diabetes in the NHANES III.

OBJECTIVE: Increasing rates of type 2 diabetes worldwide suggest that diabetes may be caused by environmental toxins. Cadmium is a widespread environmental pollutant that accumulates in the pancreas and exerts diabetogenic effects in animals. To test the hypothesis that exposure to cadmium is associated with impaired fasting glucose and type 2 diabetes, we examined the associations between urinary cadmium and the prevalence of impaired fasting glucose (prediabetes) and diabetes in the Third National Health and Nutrition Examination Survey (NHANES III). RESEARCH DESIGN AND METHODS: We analyzed data on 8,722 adults > or =40 years of age from the NHANES III (1988-1994), a cross-sectional health survey of a nationally representative sample of the noninstitutionalized civilian U.S. population. We studied urinary levels of cadmium (adjusted for urine creatinine) in relation to the prevalence of impaired fasting glucose and diabetes, using the criteria of the American Diabetes Association. RESULTS: After adjustment for age, ethnicity, sex, and BMI, the odds of impaired fasting glucose and diabetes increased dose-dependently with elevations in urinary cadmium from 0-0.99 to 1.00-1.99 and > or =2 micro g/g creatinine (impaired fasting glucose, odds ratio [OR] 1.48, 95% CI 1.21-1.82 and OR 2.05, 95% CI 1.42-2.95; diabetes, OR 1.24, 95% CI 1.06-1.45 and OR 1.45, 95% CI 1.07-1.97). CONCLUSIONS: In this large cross-sectional study, urinary cadmium levels are significantly and dose-dependently associated with both impaired fasting glucose and diabetes. These findings, which require confirmation in prospective studies, suggest that cadmium may cause prediabetes and diabetes in humans.

Authors
Schwartz, GG; Il'yasova, D; Ivanova, A
MLA Citation
Schwartz, GG, Il'yasova, D, and Ivanova, A. "Urinary cadmium, impaired fasting glucose, and diabetes in the NHANES III." Diabetes Care 26.2 (February 2003): 468-470.
PMID
12547882
Source
pubmed
Published In
Diabetes Care
Volume
26
Issue
2
Publish Date
2003
Start Page
468
End Page
470
Show More